US4628098A - 2-[2-pyridylmethylthio-(sulfinyl)]benzimidazoles - Google Patents
2-[2-pyridylmethylthio-(sulfinyl)]benzimidazoles Download PDFInfo
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- US4628098A US4628098A US06/760,568 US76056885A US4628098A US 4628098 A US4628098 A US 4628098A US 76056885 A US76056885 A US 76056885A US 4628098 A US4628098 A US 4628098A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- This invention relates to pyridine derivatives useful as e.g. anti-ulcer agents and to a method of preparing them.
- gastrointestinal ulcer is induced by unbalance between aggressive factors, e.g. hydrochloric acid, pepsin, and defensive factors, e.g. mucus secretion and mucosal blood flow. Therefore, a medicine having both an action of inhibiting gastric acid secretion and an action of enhancing protection of gastric mucosa has been desired.
- aggressive factors e.g. hydrochloric acid, pepsin, and defensive factors, e.g. mucus secretion and mucosal blood flow. Therefore, a medicine having both an action of inhibiting gastric acid secretion and an action of enhancing protection of gastric mucosa has been desired.
- the present inventors diligently studied with the purpose of preparing an anti-ulcer agent having excellent actions of inhibiting gastric acid secretion, of protecting gastric mucosa and of antagonizing ulceration. They found that a certain type of pyridine derivatives meets the said purpose, and they conducted further study to accomplish the present invention.
- the present invention relates to
- pyridine derivatives of the formula (I) ##STR2## wherein R 1 is hydrogen, methoxy or trifluoromethyl, R 2 and R 3 are independently hydrogen or methyl, R 4 is a C 2-5 fluorinated alkyl, and n denotes 0 or 1, or their pharmacologically acceptable salts and
- C 2-5 fluorinated alkyl groups shown by R 4 are exemplified by 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, 2,2,3,3-tetrafluoropropyl 1-(trifluoromethyl)-2,2,2-trifluoroethyl, 2,2,3,3,4,4,4-heptafluorobutyl and 2,2,3,3,4,4,5,5-octafluoropentyl.
- Examples of the leaving groups X 1 and X 2 in the above formulae are halogen, preferably chlorine, bromine or iodine, or a reactive esterified hydroxy group, e.g. an arylsulfonyloxy, for example, phenylsulfonyloxy or tosyloxy, or C 1-4 alkylsulfonyloxy, for example, methanesulfonyloxy, or an organic phosphoryloxy, for example, diphenylphosphoryloxy, dibenzylphosphoryloxy or di-C 1-4 alkylphosphoryloxy and the like.
- halogen preferably chlorine, bromine or iodine
- a reactive esterified hydroxy group e.g. an arylsulfonyloxy, for example, phenylsulfonyloxy or tosyloxy, or C 1-4 alkylsulfonyloxy, for example, methanesulfonyloxy, or an organic
- R 1 may be located at 4- or 5-position, and preferably at 5-position.
- the base is exemplified by alkali metal hydride e.g. sodium hydride and potassium hydride; alkali metal e.g. metallic sodium; sodium alcoholate e.g. sodium methoxide and sodium ethoxide; alkali metal carbonate e.g. potassium carbonate and sodium carbonate; and organic amines e.g. triethylamine.
- the solvent used for the reaction is exemplified by alcohols e.g.
- the amount of a base used for the reaction is usually in a little excess to the equivalent, but it may be in a large excess. Specifically, it is about 1-10 equivalents, more preferably about 1-equivalents.
- the reaction temperature ranges usually from about 0° C. to about the boiling point of the solvent then used, more preferably from about 20° C. to about 80° C.
- the reaction time ranges from about 0.2 to about 24 hours, more preferably from about 0.5 to about 2 hours.
- the oxidizing agent to be employed here is exemplified by peracid e.g. m-chloroperbenzoic acid, peracetic acid, trifluoroperacetic acid and permaleic acid, or sodium bromite or sodium hypochlorite or hydrogen peroxide.
- the solvent used for the reaction is exemplified by halogenated hydrocarbon e.g. chloroform and dichloromethane, ethers e.g. tetrahydrofuran and dioxane, amides e.g.
- the reaction temperature ranges from that under ice-cooling to about the boiling point of the solvent then employed, usually from that under ice-cooling to room temperature, more preferably from about 0° C. to about 10° C.
- the reaction time usually ranges from about 0.1 to about 24 hours, more preferably from about 0.1 to about 4 hours.
- the object compound (I) produced by the above reaction can be isolated and purified by conventional means e.g. recrystallization and chromatography.
- the compound (I) of this invention may be led to pharmacologically acceptable salts thereof by per se conventional means, the salts being exemplified by hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate, sulfate, acetate and citrate.
- a nitro compound of the formula (IV) [wherein R 2 and R 3 are of the same meaning as defined above] is allowed to react with an alcohol derivative R 4 OH (V) [wherein R 4 is of the same meaning as defined above] in the presence of a base to give an alkoxy derivative of the formula (VI) [wherein R 2 , R 3 and R 4 are of the same meaning as defined above].
- the base is exemplified by alkali metal e.g. lithium, sodium and potassium; alkali metal hydride e.g. sodium hydride and potassium hydride; alcoholate e.g. potassium t-butoxide and sodium propoxide; alkali metal carbonate or hydrogen carbonate e.g.
- the solvent used for the reaction is exemplified by, besides R 4 OH itself, ethers such as tetrahydrofuran and dioxane as well as ketones such as acetone and methyl ethyl ketone, acetonitrile, dimethylformamide and hexamethylphosphoric acid triamide.
- the reaction temperature is suitably selected within the range from those under ice-cooling to those near the boiling point of the solvent used.
- the reaction time ranges usually from about 1 to about 48 hours.
- the thus-obtained compound (VI) is subjected to heating (about 80° to about 120° C.) in the presence of acetic anhydride singly or together with a mineral acid e.g. sulfuric acid and perchloric acid to give a 2-acetoxymethylpyridine derivative of the formula (VII) [wherein R 2 , R 3 and R 4 are of the same meaning as defined above].
- the reaction time ranges usually from about 0.1 to about 10 hours.
- the compound (VII) is subjected to alkali-hydrolysis to give a 2-hydroxymethyl pyridine derivative of the formula (VIII) [wherein R 2 , R 3 and R 4 are of the same meaning as defined above].
- the alkali is exemplified by sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate.
- the solvent used for the reaction is exemplified by methanol, ethanol and water.
- the reaction temperature ranges usually from about 20° C. to about 60° C.
- the reaction time is within the range of from about 0.1 to about 2 hours.
- the compound (VIII) is further subjected to reaction with a chlorinating agent such as thionyl chloride, or an esterifying agent, e.g. an organic sulfonic acid chloride such as methanesulfonyl chloride or p-toluenesulfonyl chloride, or an organic phosphoric acid chloride such as diphenylphosphoryl chloride to give the compound (III).
- a chlorinating agent such as thionyl chloride, or an esterifying agent, e.g. an organic sulfonic acid chloride such as methanesulfonyl chloride or p-toluenesulfonyl chloride, or an organic phosphoric acid chloride such as diphenylphosphoryl chloride to give the compound (III).
- the amount of the chlorinating agent used for the reaction is usually in equivalent to a large excess relative to the compound (VIII).
- the solvent used for the reaction is exemplified by chloro
- the amount of the organic sulfonic acid chloride or organic phosphoric acid chloride used for the reaction is usually in equivalent to a little excess, and the reaction is usually conducted in the presence of a base.
- the base is exemplified by organic base e.g. triethylamine and tributylamine, or inorganic base e.g. sodium carbonate, potassium carbonate and sodium hydrogen carbonate.
- the amount of a base used for the reaction is usually in equivalent to a little excess.
- the solvent used for the reaction is exemplified by chloroform, dichloromethane, carbon tetrachloride or acetonitrile.
- the reaction temperature ranges usually from that under ice-cooling to about the boiling point of the solvent then used.
- the raction time ranges usually from a few minutes to a few hours. It is usually preferable to use the thus-produced compound (III) immediately for the reaction with a compound (II).
- the compound (X) is subjected to methylation with dimethyl sulfate to give a compound of the formula (XI) [wherein R 2 , R 3 and R 4 are of the same meaning as defined above].
- the reaction can be conducted usually without solvent.
- the reaction temperature ranges from about 100° C. to about 120° C., and the reaction time is within the range of from about 0.1 to about 4 hours.
- the compound (XI) is allowed to react with a radical source such as ammonium persulfate or any other persulfate in methanol to give the above-mentioned compound (VIII).
- a radical source such as ammonium persulfate or any other persulfate in methanol.
- the reaction temperature is within the range of from about 20° C. to about 80° C., and the reaction time ranges from about 0.5 to about 4 hours.
- the esophagus was clipped, 10 ml of 1% formalin solution was instilled into the stomach from the duodenum, and then the duodenum was clipped.
- the whole stomach waa immersed in 1% formalin solution. About 15 minutes later, the stomachs were opened along the greater curvature.
- the area of the lesions which occurred in the gastric antral mucosa was measured under a dissecting microscope with a square-grid eye piece (x10).
- the sum total of the individual lesions in each animal was measured, and the average value per group was calculated. Based on the difference between the average value of each group and that of the control group, the inhibition rate was determined.
- the test compound and indometachacin were suspended in a 5% gum arabic solution, respectively and administered in a volume of 2 ml/kg.
- the compounds of this invention have superior anti-ulcer action as compared with known compounds by about 1.5-20 times or more.
- the compound (I) of this invention shows excellent actions of inhibiting gastric acid secretion, protecting gastric mucous membrane and preventing ulceration.
- the compound (I) of this invention has an anti-ulcer action, a gastric acid secretion controlling action and a mucous membrane protecting action, furthermore is of low toxicity and is relatively stable as a chemical substance.
- the compound (I) of this invention can thus be used for prophylaxis and therapy of digestive ulcers (e.g. gastric ulcer, duodenal ulcer) and gastritis in mammalian animals (e.g. mouse, rat, rabbit, dog, cat and man).
- the compound (I) of this invention when used as an anti-ulcer agent for the therapy of digestive ulcers in mammalian animals, it can be administered orally in a dosage form of capsules, tablets, granules, etc. by formulating with a pharmacologically acceptable carrier, excipient, diluent, etc.
- the daily dose is about 0.01-30 mg/kg, more preferably about 0.1-3 mg/kg.
Abstract
The compound of the formula ##STR1## wherein R1 is hydrogen, methoxy or trifluoromethyl, R2 and R3 are independently hydrogen or methyl, R4 is a C2-5 fluorinated alkyl and n denotes 0 or 1, or a pharmacologically acceptable salt thereof is novel, and useful for prophylaxis and therapy of digestive ulcers (e.g. gastric ulcer, duodenal ulcer) and gastritis.
Description
This invention relates to pyridine derivatives useful as e.g. anti-ulcer agents and to a method of preparing them.
As the pyridine derivatives having anti-ulcer activity, those disclosed in U.S. Pat. No. 4,255,431 (Japanese Unexamined Patent Laid-open No. 141783/79) and U.S. Pat. No. 4,472,409 (Japanese Unexamined Patent Laid-open No. 135881/83) etc. have been known.
However, while these known compounds have an acid-secretion-inhibiting action, their gastric mucous membrane protecting action is insufficient, thus being hardly considered satisfactory as anti-ulcer agents. Besides, these compounds are possessed of such drawbacks in the physico-chemical properties as being unstable and readily decomposed.
It is considered that gastrointestinal ulcer is induced by unbalance between aggressive factors, e.g. hydrochloric acid, pepsin, and defensive factors, e.g. mucus secretion and mucosal blood flow. Therefore, a medicine having both an action of inhibiting gastric acid secretion and an action of enhancing protection of gastric mucosa has been desired.
The present inventors diligently studied with the purpose of preparing an anti-ulcer agent having excellent actions of inhibiting gastric acid secretion, of protecting gastric mucosa and of antagonizing ulceration. They found that a certain type of pyridine derivatives meets the said purpose, and they conducted further study to accomplish the present invention.
The present invention relates to
(1) pyridine derivatives of the formula (I) ##STR2## wherein R1 is hydrogen, methoxy or trifluoromethyl, R2 and R3 are independently hydrogen or methyl, R4 is a C2-5 fluorinated alkyl, and n denotes 0 or 1, or their pharmacologically acceptable salts and
(2) a method for preparing a compound (I) or its pharmacologically acceptable salt, which comprises allowing a compound of the formula (II) ##STR3## wherein R1 is of the same meaning as defined above, to react with a compound of the formula (III) ##STR4## wherein R2, R3 and R4 are of the same meaning as defined above, one of X1 and X2 is SH and the other is a leaving group and, when necessary, by subjecting the reaction product to oxidation.
In the above formulae, C2-5 fluorinated alkyl groups shown by R4 are exemplified by 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, 2,2,3,3-tetrafluoropropyl 1-(trifluoromethyl)-2,2,2-trifluoroethyl, 2,2,3,3,4,4,4-heptafluorobutyl and 2,2,3,3,4,4,5,5-octafluoropentyl.
Examples of the leaving groups X1 and X2 in the above formulae are halogen, preferably chlorine, bromine or iodine, or a reactive esterified hydroxy group, e.g. an arylsulfonyloxy, for example, phenylsulfonyloxy or tosyloxy, or C1-4 alkylsulfonyloxy, for example, methanesulfonyloxy, or an organic phosphoryloxy, for example, diphenylphosphoryloxy, dibenzylphosphoryloxy or di-C1-4 alkylphosphoryloxy and the like.
R1 may be located at 4- or 5-position, and preferably at 5-position.
A sulfide derivative (I) (n=0), among the object compounds of this invention, can be prepared by allowing a compound (II) to react with a compound (III). It is convenient to conduct this reaction in the presence of a base. The base is exemplified by alkali metal hydride e.g. sodium hydride and potassium hydride; alkali metal e.g. metallic sodium; sodium alcoholate e.g. sodium methoxide and sodium ethoxide; alkali metal carbonate e.g. potassium carbonate and sodium carbonate; and organic amines e.g. triethylamine. The solvent used for the reaction is exemplified by alcohols e.g. methanol and ethanol, as well as dimethylformamide. The amount of a base used for the reaction is usually in a little excess to the equivalent, but it may be in a large excess. Specifically, it is about 1-10 equivalents, more preferably about 1-equivalents. The reaction temperature ranges usually from about 0° C. to about the boiling point of the solvent then used, more preferably from about 20° C. to about 80° C. The reaction time ranges from about 0.2 to about 24 hours, more preferably from about 0.5 to about 2 hours.
A sulfinyl derivative (I) (n=1), which is also among the object compounds of this invention, can be prepared by subjecting a compound (I) (n=0) to oxidation. The oxidizing agent to be employed here is exemplified by peracid e.g. m-chloroperbenzoic acid, peracetic acid, trifluoroperacetic acid and permaleic acid, or sodium bromite or sodium hypochlorite or hydrogen peroxide. The solvent used for the reaction is exemplified by halogenated hydrocarbon e.g. chloroform and dichloromethane, ethers e.g. tetrahydrofuran and dioxane, amides e.g. dimethylformamide, alcohols, e.g. methanol, ethanol, propanol, and t-butanol or water, and these solvents may used singly or in admixture. The oxidizing agent is used preferably in approximately equivalent or a little excess amount relative to the compound (I) (n=0). Specifically, it is about 1 to about 3 equivalents, more preferably about 1-1.5 equivalent. The reaction temperature ranges from that under ice-cooling to about the boiling point of the solvent then employed, usually from that under ice-cooling to room temperature, more preferably from about 0° C. to about 10° C. The reaction time usually ranges from about 0.1 to about 24 hours, more preferably from about 0.1 to about 4 hours.
The object compound (I) produced by the above reaction can be isolated and purified by conventional means e.g. recrystallization and chromatography.
The compound (I) of this invention may be led to pharmacologically acceptable salts thereof by per se conventional means, the salts being exemplified by hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate, sulfate, acetate and citrate.
Among the compounds (I), those of n=0 give stable salts, while those of n=1 may exist as an aqueous solution though unstable.
The process of preparing the starting material (III) is described as follows.
(Process 1) ##STR5##
A nitro compound of the formula (IV) [wherein R2 and R3 are of the same meaning as defined above] is allowed to react with an alcohol derivative R4 OH (V) [wherein R4 is of the same meaning as defined above] in the presence of a base to give an alkoxy derivative of the formula (VI) [wherein R2, R3 and R4 are of the same meaning as defined above]. The base is exemplified by alkali metal e.g. lithium, sodium and potassium; alkali metal hydride e.g. sodium hydride and potassium hydride; alcoholate e.g. potassium t-butoxide and sodium propoxide; alkali metal carbonate or hydrogen carbonate e.g. potassium carbonate, lithium carbonate, sodium carbonate, potassium hydrogen carbonate and sodium hydrogen carbonate; or alkali hydroxide e.g. sodium hydroxide and potassium hydroxide. The solvent used for the reaction is exemplified by, besides R4 OH itself, ethers such as tetrahydrofuran and dioxane as well as ketones such as acetone and methyl ethyl ketone, acetonitrile, dimethylformamide and hexamethylphosphoric acid triamide. The reaction temperature is suitably selected within the range from those under ice-cooling to those near the boiling point of the solvent used. The reaction time ranges usually from about 1 to about 48 hours.
The thus-obtained compound (VI) is subjected to heating (about 80° to about 120° C.) in the presence of acetic anhydride singly or together with a mineral acid e.g. sulfuric acid and perchloric acid to give a 2-acetoxymethylpyridine derivative of the formula (VII) [wherein R2, R3 and R4 are of the same meaning as defined above]. The reaction time ranges usually from about 0.1 to about 10 hours.
Then, the compound (VII) is subjected to alkali-hydrolysis to give a 2-hydroxymethyl pyridine derivative of the formula (VIII) [wherein R2, R3 and R4 are of the same meaning as defined above]. The alkali is exemplified by sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate. The solvent used for the reaction is exemplified by methanol, ethanol and water. The reaction temperature ranges usually from about 20° C. to about 60° C. The reaction time is within the range of from about 0.1 to about 2 hours.
The compound (VIII) is further subjected to reaction with a chlorinating agent such as thionyl chloride, or an esterifying agent, e.g. an organic sulfonic acid chloride such as methanesulfonyl chloride or p-toluenesulfonyl chloride, or an organic phosphoric acid chloride such as diphenylphosphoryl chloride to give the compound (III). The amount of the chlorinating agent used for the reaction is usually in equivalent to a large excess relative to the compound (VIII). The solvent used for the reaction is exemplified by chloroform, dichloromethane and tetrachloroethane. The reaction temperature is usually within the range of from about 20° C. to about 80° C., and the reaction time is about 0.1 to about 2 hours.
The amount of the organic sulfonic acid chloride or organic phosphoric acid chloride used for the reaction is usually in equivalent to a little excess, and the reaction is usually conducted in the presence of a base. The base is exemplified by organic base e.g. triethylamine and tributylamine, or inorganic base e.g. sodium carbonate, potassium carbonate and sodium hydrogen carbonate. The amount of a base used for the reaction is usually in equivalent to a little excess. The solvent used for the reaction is exemplified by chloroform, dichloromethane, carbon tetrachloride or acetonitrile. The reaction temperature ranges usually from that under ice-cooling to about the boiling point of the solvent then used. The raction time ranges usually from a few minutes to a few hours. It is usually preferable to use the thus-produced compound (III) immediately for the reaction with a compound (II).
(Process 2) ##STR6##
By a reaction similar to the above-described process (1), a compound of the formula (IX) [wherein R2 and R3 are of the same meaning as defined above] is led to a compound of the formula (X) [wherein R2, R3 and R4 are of the same meaning as defined above].
Then, the compound (X) is subjected to methylation with dimethyl sulfate to give a compound of the formula (XI) [wherein R2, R3 and R4 are of the same meaning as defined above]. The reaction can be conducted usually without solvent. The reaction temperature ranges from about 100° C. to about 120° C., and the reaction time is within the range of from about 0.1 to about 4 hours.
Further, the compound (XI) is allowed to react with a radical source such as ammonium persulfate or any other persulfate in methanol to give the above-mentioned compound (VIII). The reaction temperature is within the range of from about 20° C. to about 80° C., and the reaction time ranges from about 0.5 to about 4 hours.
Pharmacological actions of the compounds of the present invention are described as follows.
As the models of gastrointestinal ulcers, restraint and water-immersion stress-induced ulcer, indomethacin-induced ulcer and ethanol-induced gastric mucosal lesions have been used. However, as a model mimicking human gastric ulcer, indomethacin-induced gastric antral ulcer was reported in "Gastroenterology" (Satoh et al. 81, p. 719, 1981), which is considered to be of value as an experimental model. Therefore, the following are data of anti-ulcer actions of the object compounds (I) and of some representable known compounds, on the ulcer model in the above-mentioned literature reference. Experimental Method:
Male Sprague-Dawley rats of 7-weeks old were fasted for 24 hours. These animals were administered test compounds into stomach by using a gastric tube. After 30 minutes, indomethacin, 30 mg/kg subcutaneously, was administered. During 30-90 minutes after the administration of indomethacin, these animals had free access to chow pellets (Japan Clea, CE-2). At 5 hours after the administration of indomethacin, 1 ml of 1% Evans blue was injected to the animals via the tail vein, followed by sacrificing these animals with carbon dioxide gas. The stomach was removed together with the lower part of esophagus and the duodenum. The esophagus was clipped, 10 ml of 1% formalin solution was instilled into the stomach from the duodenum, and then the duodenum was clipped. The whole stomach waa immersed in 1% formalin solution. About 15 minutes later, the stomachs were opened along the greater curvature. The area of the lesions which occurred in the gastric antral mucosa was measured under a dissecting microscope with a square-grid eye piece (x10). The sum total of the individual lesions in each animal was measured, and the average value per group was calculated. Based on the difference between the average value of each group and that of the control group, the inhibition rate was determined. The test compound and indometachacin were suspended in a 5% gum arabic solution, respectively and administered in a volume of 2 ml/kg.
______________________________________
Experimental Results:
##STR7##
Anti-ulcer action.sup.(a)
R.sup.1
R.sup.2
R.sup.3
R.sup.4 n ID.sub.50 (mg/kg, p.o.)
______________________________________
H H H CH.sub.2 CF.sub.3
1 2.4
H CH.sub.3
H CH.sub.2 CF.sub.3
1 <1.0
H H H CH.sub.2 CF.sub.2 CF.sub.3
1 1.3
H CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.3
1 <1.0
H H H CH.sub.2 CF.sub.2 CF.sub.2 H
1 1.3
H CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.2 H
1 <1.0
H CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.3
0 3.7
5-OCH.sub.3
CH.sub.3
CH.sub.3
CH.sub.3 *.sup.1
21.0
5-CF.sub.3
CH.sub.3
H CH.sub.3 *.sup.2
5.5
______________________________________
*.sup.1 The compound disclosed in Example 23 of USP. 4,255,431 (Japanese
Unexamined Patent Laidopen No. 141783/1979)
*.sup.2 The compound disclosed in Example 3 of USP. 4,472,409 (Japanese
Unexamined Patent Laidopen No. 135881/1983)
.sup.(a) Using 6 rats per group, each of the test compounds was
administered in a dose of 1, 3, 10 and 30 mg/kg to determine ID.sub.50.
As shown by the above data, the compounds of this invention have superior anti-ulcer action as compared with known compounds by about 1.5-20 times or more. Besides, the compound (I) of this invention shows excellent actions of inhibiting gastric acid secretion, protecting gastric mucous membrane and preventing ulceration.
Regarding about the toxicity of the compound (I) of this invention, oral administration of the compound employed for the experiment of anti-ulceration (compound of R1 =H, R2 =CH3, R3 =H, R4 =CH2 CF2 CF3, n=1) to mice even in a dose of 2000 mg/kg caused no fatal effect; thus the compound (I) is low in toxicity.
As described in the foregoing, the compound (I) of this invention has an anti-ulcer action, a gastric acid secretion controlling action and a mucous membrane protecting action, furthermore is of low toxicity and is relatively stable as a chemical substance. The compound (I) of this invention can thus be used for prophylaxis and therapy of digestive ulcers (e.g. gastric ulcer, duodenal ulcer) and gastritis in mammalian animals (e.g. mouse, rat, rabbit, dog, cat and man).
When the compound (I) of this invention is used as an anti-ulcer agent for the therapy of digestive ulcers in mammalian animals, it can be administered orally in a dosage form of capsules, tablets, granules, etc. by formulating with a pharmacologically acceptable carrier, excipient, diluent, etc. The daily dose is about 0.01-30 mg/kg, more preferably about 0.1-3 mg/kg.
Incidentally, the compound of this invention (I) (n=0) is useful as a starting material for preparing the compound (I) (n=1).
The processes of producing the starting compounds to be employed in the method of this invention as well as those of producing the compound (I) of this invention are specifically explained by the following Reference Examples and Working Examples.
In 2,2,3,3-tetrafluoropropanol (10 ml) was dissolved 2,3-dimethyl-4-nitropyridine-1-oxide (2 g). To the solution was added potassium t-butoxide (1.6 g) little by little at room temperature. The mixture was then heated at 80°-90° C. for 22 hours. The reaction solution was diluted with water, which was subjected to extraction with chloroform. The extract was dried on magnesium sulfate, and then concentrated. The concentrate was chromatographed on a column of silica gel (70 g). Elution was conducted with methanol-chloroform (1:10), and then subjected to recrystallization from ethyl acetate-hexane to yield 2.6 g of 2,3-dimethyl-4-(2,2,3,3-tetrafluoropropoxy)pyridine-1-oxide as colorless needles, m.p. 138°-139° C.
After the manner above, compounds (VI) were prepared from compounds (IV).
______________________________________
Compound (VI)
R.sup.2 R.sup.3 R.sup.4 Melting point (°C.)
______________________________________
H H CH.sub.2 CF.sub.3
148-150
CH.sub.3 CH.sub.3 CH.sub.2 CF.sub.3
138-139
______________________________________
A mixture of 2,3-dimethyl-4-nitropyridine-1-oxide (2.0 g), methyl ethyl ketone (30 ml), 2,2,3,3,3-pentafluoropropanol (3.05 ml), anhydrous potassium carbonate (3.29 g) and hexamethyl phosphoric acid triamide (2.07 g) was heated at 70°-80° C. for 4.5 days under stirring, then insolubles were filtered off. The filtrate was concentrated, to which was added water. The mixture was subjected to extraction with ethyl acetate. The extract solution was dried on magnesium sulfate, followed by removing the solvent by evaporation. The residue was chromatographed on a column of silica gel (50 g), eluted with chloroform-methanol (10:1), and recrystallized from ethyl acetate-hexane to yield 2.4 g of 2,3-dimethyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine-1-oxide as colorless needles, m.p. 148°-149° C.
By this process, compounds (VI) were prepared from starting compounds (IV).
______________________________________
Compound (VI)
R.sup.2 R.sup.3 R.sup.4 Melting point (°C.)
______________________________________
CH.sub.3
H CH.sub.2 CF.sub.3
131.0-131.5
H CH.sub.3 CH.sub.2 CF.sub.3
153-154
H H CH.sub.2 CF.sub.2 CF.sub.3
79-81
H CH.sub.3 CH.sub.2 CF.sub.2 CF.sub.3
140-142
H H CH.sub.2 CF.sub.2 CF.sub.2 H
Oily
H CH.sub.3 CH.sub.2 CF.sub.2 CF.sub.2 H
143.5-144.5
CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.2 H
138-139
______________________________________
Concentrated sulfuric acid (two drops) was added to a solution of 2,3-dimethyl-4-(2,2,3,3-tetrafluoropropoxy)pyridine-1-oxide (2.6 g) in acetic anhydride (8 ml). The mixture was stirred at 110° C. for 4 hours, which was then concentrated. The residue was dissolved in methanol (20 ml), to which was added sodium hydroxide (1.2 g) dissolved in water (5 ml). The mixture was stirred at room temperature for 30 minutes, which was concentrated. To the residue was added water, and the mixture was subjected to extraction with ethyl acetate. The extract was dried on magnesium sulfate, followed by removal of the solvent by evaporation. The residue was chromatographed on a column of silica gel (50 g), eluted with chloroform-methanol (10:1), and recrystallized from isopropyl ether to yield 1.6 g of 2-hydroxymethyl-3-methyl-4-(2,2,3,3-tetrafluoropropoxy)pyridine as yellow crystals, m.p. 67°-68° C.
By this process, compounds (VIII) were prepared from compounds (VI).
______________________________________
Compound (VIII)
R.sup.2 R.sup.3 R.sup.4 Melting point (°C.)
______________________________________
H H CH.sub.2 CF.sub.3
Oily
CH.sub.3
H CH.sub.2 CF.sub.3
93.5-94.0
H H CH.sub.2 CF.sub.2 CF.sub.3
Oily
CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.3
Oily
H CH.sub.3 CH.sub.2 CF.sub.2 CF.sub.3
87-89
H H CH.sub.2 CF.sub.2 CF.sub.2 H
88-89
H CH.sub.3 CH.sub.2 CF.sub.2 CF.sub.2 H
98-99
CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.2 H
67-68
______________________________________
To a solution of 3,5-dimethyl-4-nitropyridine-1-oxide (2.0 g) in 2,2,3,3,3-pentafluoropropanol (10 g) was added at 0° C. little by little potassium t-butoxide (2 g) over 15 minutes. The mixture was stirred at 60° C. for 18 hours. To the reaction mixture was added chloroform, which was subjected to filtration with celite. The filtrate was chromatographed on a column of silica gel (80 g), eluted with ethyl acetate-hexane (1:1), then with 20% methanol-ethyl acetate, and recrystallized from ether-hexane to yield 2.6 g of 3,5-dimethyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine-1-oxide as crystals, m.p. 89°-91° C.
By this process, compounds (X) were prepared from compounds (IX).
______________________________________
Compound (X)
R.sup.2 R.sup.3 R.sup.4 Melting point (°C.)
______________________________________
CH.sub.3 H CH.sub.2 CF.sub.3
82-94
CH.sub.3 CH.sub.3 CH.sub.2 CF.sub.3
138-139
______________________________________
A mixture of 3,5-dimethyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine-1-oxide (2.5 g) and dimethyl sulfate (1 ml) was heated at 120° C. for 30 minutes, to which was then added methanol (12.5 ml). To the mixture was added dropwise at 80° C. ammonium persulfate (4.3 g) dissolved in water (20 ml)-methanol (10 ml) over 30 minutes, which was stirred for further 30 minutes. The resultant solution was concentrated. To the residue was added ice, which was neutralized with sodium carbonate, followed by extraction with chloroform. The extract was dried on sodium sulfate, followed by removing the solvent by evaporation to give 2.2 g of 3,5-dimethyl-2-hydroxymethyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine as an oily substance.
By this process, compounds (VIII) were prepared from compounds (X).
______________________________________
Compound (VIII)
R.sup.2 R.sup.3 R.sup.4 Melting point (°C.)
______________________________________
H CH.sub.3 CH.sub.2 CF.sub.3
116-119
CH.sub.3 CH.sub.3 CH.sub.2 CF.sub.3
62-63
______________________________________
To a solution of 2-hydroxymethyl-3-methyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine (350 mg) in chloroform (10 ml) was added thionyl chloride (0.2 ml). The mixture was refluxed for 30 minutes, which was then concentrated. The residue was dissolved in methanol (5 ml). The solution was added to a mixture of 2-mercaptobenzimidazole (200 mg), 28% sodium methoxide solution (1 ml) and methanol (6 ml), which was refluxed for 30 minutes. From the resultant was removed methanol by evaporation. To the residue was added water, which was subjected to extraction with ethyl acetate. The extract was washed with a dilute sodium hydroxide solution, followed by drying on magnesium sulfate. From the resultant was removed the solvent by evaporation. The residue was then chromatographed on a column of silica gel (20 g), eluted with ethyl acetate-hexane (2:1), and then recrystallized from ethyl acetate-hexane to yield 370 mg of 2-[3-methyl-4-(2,2,3,3,3-pentafluoropropoxy)-pyrid-2-yl]methylthiobenzimidazole.1/2 hydrate as colorless plates, m.p. 145°-146° C.
By this process, compounds (I) (n=0) were prepared by allowing compounds (II) to react with compounds (III).
______________________________________
Compound (I) (n = 0)
R.sup.1
R.sup.2 R.sup.3
R.sup.4 Melting point (°C.)
______________________________________
H H H CH.sub.2 CF.sub.3
138-139
H CH.sub.3
H CH.sub.2 CF.sub.3
149-150
H H CH.sub.3
CH.sub.2 CF.sub.3
168-170
H CH.sub.3
CH.sub.3
CH.sub.2 CF.sub.3
151.5-152.0
H H H CH.sub.2 CF.sub.2 CF.sub.3
125-126
H H CH.sub.3
CH.sub.2 CF.sub.2 CF.sub.3
151-152
H H H CH.sub.2 CF.sub.2 CF.sub.2 H
Oily*.sup.3
H CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.2 H
134-135
H H CH.sub.3
CH.sub.2 CF.sub.2 CF.sub.2 H
148-149
H CH.sub.3
CH.sub.3
CH.sub.2 CF.sub.2 CF.sub.3
158-160
*.sup.4 5-CF.sub.3
CH.sub.3
H CH.sub.2 CF.sub.3
92-93
5-OCH.sub.3
CH.sub.3
H CH.sub.2 CF.sub.3
159-160
5-OCH.sub.3
H H CH.sub.2 CF.sub.3
152-153
______________________________________
*.sup.3 NMR spectrum (CDCl.sub.3)δ: 4.35(S), 4.39 (t,t,J=1.5 and 12
Hz), 5.98 (1H,t,t,J=52.5 and 4 Hz), 6.81 (1H,d,d,J=2 and 6 Hz) 6.95
(1H,d,J=2Hz), 7.1-7.3 (2H,m), 7.4-7.7 (2H,m), 8.50 (1H,d,J=6 Hz)
*.sup.4 1/4H.sub.2 O (crystal water)
To a solution of 2-[3-methyl-4-(2,2,3,3,3,-pentafluoropropoxy)pyrid-2-yl-methylthiobenzimidazole (2.2 g) in chloroform (20 ml) was added dropwise under ice-cooling over a period of 30 minutes m-chloroperbenzoic acid (1.3 g) dissolved in chloroform (15 ml). The solution was washed with a saturated aqueous solution of sodium hydrogen carbonate, then dried on magnesium sulfate, and concentrated. The residue was chromatographed on a column of silica gel (50 g), eluted with ethyl acetate, and then recrystallized from aceton-isopropyl ether to give 1.78 g of 2-[3-methyl-4-(2,2,3,3,3-pentafluoropropxy)pyrid-2-yl]methylsulfinylbenzimidazole as pale yellow prisms, m.p. 161°-163° C. (decomp.).
By this process, compounds (I) (n=1) were prepared from compounds (I) (n=0).
______________________________________
Compound (I) (n = 1)
R.sup.1
R.sup.2 R.sup.3
R.sup.4 Melting point (°C.)
______________________________________
H H H CH.sub.2 CF.sub.3
176-177
H CH.sub.3
H CH.sub.2 CF.sub.3
178-182(d)
H H CH.sub.3
CH.sub.2 CF.sub.3
175-177(d)
H CH.sub.3
CH.sub.3
CH.sub.2 CF.sub.3
177-178(d)
H H H CH.sub.2 CF.sub.2 CF.sub.3
148-150(d)
H H CH.sub.3
CH.sub.2 CF.sub.2 CF.sub.3
145-148(d)
H H H CH.sub.2 CF.sub.2 CF.sub.2 H
132-133
H CH.sub.3
H CH.sub.2 CF.sub.2 CF.sub.2 H
147-148(d)
H H CH.sub.3
CH.sub.2 CF.sub.2 CF.sub.2 H
136-139(d)
H CH.sub.3
CH.sub.3
CH.sub.2 CF.sub.2 CF.sub.3
157-159
5-CF.sub.3
CH.sub.3
H CH.sub.2 CF.sub.3
161-162(d)
5-OCH.sub.3
CH.sub.3
H CH.sub.2 CF.sub.3
140.5-142(d)
5-OCH.sub.3
H H CH.sub.2 CF.sub.3
162-163(d)
______________________________________
(Note) (d): decomposition
Claims (36)
1. A compound of the formula ##STR8## wherein R1 is hydrogen, methoxy or trifluoromethyl, R2 and R3 are independently hydrogen or methyl, R4 is a C2-5 fluorinated alkyl and n denotes 0 or 1, and a pharmacologically acceptable salt thereof.
2. A compound according to claim 1, wherein R1 is hydrogen.
3. A compound according to claim 1, wherein R1 is methoxy.
4. A compound according to claim 1, wherein R2 is hydrogen.
5. A compound according to claim 1, wherein R2 is methyl.
6. A compound according to claim 1, wherein R3 is hydrogen.
7. A compound according to claim 1, wherein R3 is methyl.
8. A compound according to claim 1, wherein R4 is a C2-3 fluorinated alkyl.
9. A compound according to claim 1, wherein the compound is 2-[4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylsulfinylbenzimidazole.
10. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylsulfinylbenzimidazole.
11. A compound according to claim 1, wherein the compound is 2-[4-(2,2,2-trifluoroethoxy)-5-methyl-pyrid-2-yl]methylsulfinylbenzimidazole.
12. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-5-methyl-pyrid-2-yl]methylsulfinylbenzimidazole.
13. A compound according to claim 1, wherein the compound is 2-[4-(2,2,3,3,3-pentafluoropropoxy)-pyrid-2-yl]methylsulfinylbenzimidazole
14. A compound according to claim 1, wherein the compound is 2-[4-(2,2,3,3,3-pentafluoropropoxy)-5-methyl-pyrid-2-yl]methylsulfinylbenzimidazole.
15. A compound according to claim 1, wherein the compound is 2-[4-(2,2,3,3-tetrafluoropropoxy)-pyrid-2-yl]methylsulfinylbenzimidazole.
16. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,3,3,3-pentafluoropropoxy)-pyrid-2-yl]methylsulfinylbenzimidazole.
17. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,3,3-tetrafluoropropoxy)-pyrid-2-yl]methylsulfinylbenzimidazole.
18. A compound according to claim 1, wherein the compound is 2-[5-methyl-4-(2,2,3,3-tetrafluoropropoxy)-pyrid-2-yl]methylsulfinylbenzimidazole.
19. A compound according to claim 1, wherein the compound is 2-[3,5-dimethyl-4-(2,2,3,3,3-pentafluoropropoxy)-pyrid-2-yl]methylsulfinylbenzimidazole.
20. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylsulfinyl-5-trifluoromethylbenzimidazole.
21. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylsulfinyl-5-methoxybenzimidazole.
22. A compound according to claim 1, wherein the compound is 2-[4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]-methylsulfinyl-5-methoxybenzimidazole.
23. A compound according to claim 1, wherein the compound is 2-[4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]-methylthiobenzimidazole.
24. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylthiobenzimidazole.
25. A compound according to claim 1, wherein the compound is 2-[5-methyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylthiobenzimidazole.
26. A compound according to claim 1, wherein the compound is 2-[3,5-dimethyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylthiobenzimidazole.
27. A compound according to claim 1, wherein the compound is 2-[4-(2,2,3,3,3-pentafluoropropoxy)-pyrid-2-yl]methylthiobenzimidazole.
28. A compound according to claim 1, wherein the compound is 2-[5-methyl-4-(2,2,3,3,3-pentafluoropropoxy)-pyrid-2-yl]methylthiobenzimidazole.
29. A compound according to claim 1, wherein the compound is 2-[4-(2,2,3,3-tetrafluoropropoxy)-pyrid-2-yl]methylthiobenzimidazole.
30. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,3,3-tetrafluoropropoxy)-pyrid-2-yl]methylthiobenzimidazole.
31. A compound according to claim 1, wherein the compound is 2-[5-methyl-4-(2,2,3,3-tetrafluoropropoxy)-pyrid-2-yl]methylthiobenzimidazole.
32. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,3,3,3-pentafluoropropoxy)-pyrid-2-yl]methylthiobenzimidazole.
33. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,3,3,3-pentafluoropropoxy)-5-methyl-pyrid-2-yl]methylthiobenzimidazole.
34. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl-methylthio-5-trifluoromethylbenzimidazole.
35. A compound according to claim 1, wherein the compound is 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-pyrid-2-yl-methylthio-5-methoxybenzimidazole.
36. A compound according to claim 1, wherein the compound is 2-[4-(2,2,2-trifluoroethoxy)-pyrid-2-yl]methylthio-5-methoxybenzimidazole.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59-171069 | 1984-08-16 | ||
| JP59171069A JPS6150978A (en) | 1984-08-16 | 1984-08-16 | Pyridine derivative and preparation thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US06/937,193 Continuation-In-Part US4689333A (en) | 1984-08-16 | 1986-12-02 | 2-(2-pyridylmethylthio (sulfinyl)) benzimidazoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US4628098A true US4628098A (en) | 1986-12-09 |
Family
ID=15916456
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US06/760,568 Expired - Lifetime US4628098A (en) | 1984-08-16 | 1985-07-29 | 2-[2-pyridylmethylthio-(sulfinyl)]benzimidazoles |
| US06/937,193 Expired - Lifetime US4689333A (en) | 1984-08-16 | 1986-12-02 | 2-(2-pyridylmethylthio (sulfinyl)) benzimidazoles |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US06/937,193 Expired - Lifetime US4689333A (en) | 1984-08-16 | 1986-12-02 | 2-(2-pyridylmethylthio (sulfinyl)) benzimidazoles |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US4628098A (en) |
| EP (1) | EP0174726B1 (en) |
| JP (1) | JPS6150978A (en) |
| KR (1) | KR920002128B1 (en) |
| AU (1) | AU570130B2 (en) |
| BG (1) | BG60415B2 (en) |
| CA (1) | CA1255314A (en) |
| DE (3) | DE19975017I2 (en) |
| DK (1) | DK171340B1 (en) |
| ES (1) | ES8607288A1 (en) |
| GE (1) | GEP19960313B (en) |
| GR (1) | GR851981B (en) |
| HK (1) | HK4792A (en) |
| HU (1) | HU195210B (en) |
| IE (1) | IE58363B1 (en) |
| MX (1) | MX9203043A (en) |
| NL (1) | NL930109I2 (en) |
| NO (2) | NO163131C (en) |
| PH (1) | PH20946A (en) |
| SG (1) | SG103291G (en) |
| SU (1) | SU1507211A3 (en) |
| UA (1) | UA7140A1 (en) |
| ZA (1) | ZA856117B (en) |
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| US6664276B2 (en) | 1999-06-17 | 2003-12-16 | Takeda Chemical Industries, Ltd. | Benzimidazole compound crystal |
| US20030236411A1 (en) * | 2001-09-18 | 2003-12-25 | Masaaki Nagasawa | Benzimidazole derivatives |
| US20040024014A1 (en) * | 2002-08-01 | 2004-02-05 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| US20040041229A1 (en) * | 2002-06-18 | 2004-03-04 | Chol Young-Chul | Power semiconductor device having high breakdown voltage, low on-resistance, and small switching loss and method of forming the same |
| US20040077688A1 (en) * | 1998-07-22 | 2004-04-22 | Sepracor Inc. | Hydroxylansoprazole methods |
| US20040102484A1 (en) * | 2002-07-19 | 2004-05-27 | Michael Garst | Prodrugs of proton pump inhibitors |
| WO2004046135A1 (en) * | 2002-11-18 | 2004-06-03 | Teva Pharmaceutical Industries Ltd. | Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| US6780880B1 (en) | 1999-08-26 | 2004-08-24 | Robert R. Whittle | FT-Raman spectroscopic measurement |
| WO2004072061A1 (en) * | 2003-02-05 | 2004-08-26 | Teva Pharmaceutical Industries Ltd. | Method of stabilizing lansoprazole |
| US20040177804A1 (en) * | 2002-12-19 | 2004-09-16 | Nina Finkelstein | Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates |
| US20040224989A1 (en) * | 1999-01-29 | 2004-11-11 | Barberich Timothy J. | S-lansoprazole compositions and methods |
| US20040235904A1 (en) * | 2003-03-12 | 2004-11-25 | Nina Finkelstein | Crystalline and amorphous solids of pantoprazole and processes for their preparation |
| US20040248941A1 (en) * | 2001-09-25 | 2004-12-09 | Keiji Kamiyama | Benzimidazone compound, process for producing the same, and use thereof |
| US20040266828A1 (en) * | 1999-02-26 | 2004-12-30 | Nitromed, Inc. | Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use |
| US20040265370A1 (en) * | 2003-06-26 | 2004-12-30 | Isa Odidi | Oral multi-functional pharmaceutical capsule preparations of proton pump inhibitors |
| US20050031696A1 (en) * | 2003-04-22 | 2005-02-10 | Dr. Reddy's Laboratories Limited | Oral pharmaceutical formulations of acid-labile active ingredients and process for making same |
| US20050038076A1 (en) * | 2003-07-15 | 2005-02-17 | Garst Michael E. | Process for preparing isomerically pure prodrugs of proton pump inhibitors |
| US20050049282A1 (en) * | 2001-12-18 | 2005-03-03 | Astrazeneca Ab | Process |
| US20050075370A1 (en) * | 2003-06-10 | 2005-04-07 | Viviana Braude | Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole |
| US20050075371A1 (en) * | 2003-10-03 | 2005-04-07 | Allergan, Inc. | Methods and compositions for the oral administration of prodrugs of proton pump inhibitors |
| US6909004B2 (en) | 2002-08-21 | 2005-06-21 | Teva Pharmaceutical Industries Ltd. | Method for the purification of lansoprazole |
| US20050214372A1 (en) * | 2004-03-03 | 2005-09-29 | Simona Di Capua | Stable pharmaceutical composition comprising an acid labile drug |
| US20050220870A1 (en) * | 2003-02-20 | 2005-10-06 | Bonnie Hepburn | Novel formulation, omeprazole antacid complex-immediate release for rapid and sustained suppression of gastric acid |
| US20050232992A1 (en) * | 2003-09-03 | 2005-10-20 | Agi Therapeutics Limited | Proton pump inhibitor formulations, and methods of preparing and using such formulations |
| US20050249806A1 (en) * | 2004-02-10 | 2005-11-10 | Santarus, Inc. | Combination of proton pump inhibitor, buffering agent, and nonsteroidal anti-inflammatory drug |
| US20060024362A1 (en) * | 2004-07-29 | 2006-02-02 | Pawan Seth | Composition comprising a benzimidazole and process for its manufacture |
| US20060034937A1 (en) * | 1999-11-23 | 2006-02-16 | Mahesh Patel | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| US20060057195A1 (en) * | 2002-10-16 | 2006-03-16 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| WO2006030936A1 (en) | 2004-09-13 | 2006-03-23 | Takeda Pharmaceutical Company Limited | Method and apparatus for producing oxidized compound |
| US20060173045A1 (en) * | 2003-03-13 | 2006-08-03 | Shouichi Miyawaki | Preventative or remedy for grinding |
| US20060241037A1 (en) * | 2003-10-03 | 2006-10-26 | Allergan Inc. | Compositions comprising trefoil factor family peptides and/or mucoadhesives and proton pump ihhibitor prodrugs |
| WO2006132217A1 (en) | 2005-06-07 | 2006-12-14 | Takeda Pharmaceutical Company Limited | Crystal of salt of benzimidazole compound |
| EP1743893A1 (en) | 2002-11-18 | 2007-01-17 | Teva Pharmaceutical Industries Ltd. | Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| US20070060621A1 (en) * | 2004-02-18 | 2007-03-15 | Hughes Patrick M | Methods and compositions for the administration of prodrugs of proton pump inhibitors |
| US20070082929A1 (en) * | 2005-10-06 | 2007-04-12 | Gant Thomas G | Inhibitors of the gastric H+, K+-atpase with enhanced therapeutic properties |
| WO2007074909A1 (en) | 2005-12-28 | 2007-07-05 | Takeda Pharmaceutical Company Limited | Controlled release solid preparation |
| US20070161679A1 (en) * | 2004-02-18 | 2007-07-12 | Allergan, Inc. | Method and compositions for the intravenous administration of compounds related to proton pump inhibitors |
| KR100771659B1 (en) | 2005-03-23 | 2007-10-30 | 주식회사 카이로제닉스 | Method of Preparing Pantoprazole and Its Intermediate |
| WO2008067037A2 (en) | 2006-10-05 | 2008-06-05 | Santarus, Inc. | Novel formulations of proton pump inhibitors and methods of using these formulations |
| WO2008080092A2 (en) | 2006-12-22 | 2008-07-03 | Ironwood Pharmaceuticals, Inc. | Compositions comprising bile acid sequestrants for treating esophageal disorders |
| US20080160106A1 (en) * | 2004-02-12 | 2008-07-03 | Istituto Superiore De Sanita | Novel Uses for Proton Pump Inhibitors |
| WO2008081891A1 (en) | 2006-12-28 | 2008-07-10 | Takeda Pharmaceutical Company Limited | Orally disintegrating solid preparation |
| WO2008087665A2 (en) * | 2007-01-18 | 2008-07-24 | Matrix Laboratories Ltd | Process for preparation of lansoprazole |
| US20080194307A1 (en) * | 2007-02-13 | 2008-08-14 | Jeff Sanger | Sports-based game of chance |
| US20090036406A1 (en) * | 2005-06-13 | 2009-02-05 | Takeda Pharmaceutical Company Limited | Injection |
| WO2009105568A1 (en) | 2008-02-20 | 2009-08-27 | The Curators Of The University Of Missouri | Composition comprising a combination of omeprazole and lansoprazole, and a buffering agent, and methods of using same |
| US20090227633A1 (en) * | 2008-03-04 | 2009-09-10 | Bassam Damaj | Methods to inhibit tumor cell growth by using proton pump inhibitors |
| US20090263475A1 (en) * | 2008-04-21 | 2009-10-22 | Nagaraju Manne | Dexlansoprazole compositions |
| US20090306393A1 (en) * | 2005-12-17 | 2009-12-10 | Pliva Hrvatska D.O.O. | Process for preparing of, impurities free, substituted 2-benzimidazole-sulfoxide compound |
| US20100010230A1 (en) * | 2006-09-22 | 2010-01-14 | Orchid Chemicals & Pharmaceuticals Limited | Method for the purification of lansoprazole |
| US20100093747A1 (en) * | 2008-10-10 | 2010-04-15 | Erica Brook Goodhew | Method of inducing negative chemotaxis |
| US20100113527A1 (en) * | 2008-09-30 | 2010-05-06 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of dexlansoprazole |
| WO2010079504A2 (en) | 2008-05-14 | 2010-07-15 | Watson Pharma Private Limited | Stable r(+)-lansoprazole amine salt and a process for preparing the same |
| US20100210847A1 (en) * | 2007-07-17 | 2010-08-19 | Ranbaxy Laboratories Limited | Process for the preparation of pantoprazole sodium and pantoprazole sodium sesquihydrate |
| WO2010122583A2 (en) | 2009-04-24 | 2010-10-28 | Rubicon Research Private Limited | Oral pharmaceutical compositions of acid labile substances |
| US20100280077A1 (en) * | 2007-12-18 | 2010-11-04 | Watson Pharma Private Limited | Process for Preparation of Stable Amorphous R-Lansoprazole |
| WO2010134099A1 (en) | 2009-05-21 | 2010-11-25 | Cadila Healthcare Limited | One pot process for preparing omeprazole and related compounds |
| US20100297226A1 (en) * | 2006-06-01 | 2010-11-25 | Dexcel Pharma Technologies Ltd. | Multiple unit pharmaceutical formulation |
| EP2258351A2 (en) | 2001-10-17 | 2010-12-08 | Takeda Pharmaceutical Company Limited | Granules containing lansoprazole in large amount |
| US20100317689A1 (en) * | 2006-09-19 | 2010-12-16 | Garst Michael E | Prodrugs of proton pump inhibitors including the 1h-imidazo[4,5-b] pyridine moiety |
| US7863330B2 (en) | 2006-06-14 | 2011-01-04 | Rottapharm S.P.A. | Deloxiglumide and proton pump inhibitor combination in the treatment of gastrointestinal disorders |
| WO2011004387A2 (en) | 2009-06-18 | 2011-01-13 | Matrix Laboratories Ltd | Process for the preparation of dexlansoprazole polymorphic forms |
| EP2275088A2 (en) | 2005-02-25 | 2011-01-19 | Takeda Pharmaceutical Company Limited | Method for producing granules |
| EP2277510A2 (en) | 2002-10-16 | 2011-01-26 | Takeda Pharmaceutical Company Limited | Controlled release preparation |
| EP2292612A2 (en) | 2007-12-31 | 2011-03-09 | Takeda Pharmaceutical Company Limited | Crystalline solvated forms of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole |
| EP2301556A1 (en) | 2001-03-27 | 2011-03-30 | Pro-Pharmaceuticals, Inc. | Co-Administration of a Polysaccharide with a Chemotherapeutic Agent for the Treatment of Cancer |
| EP2345650A1 (en) | 2000-12-01 | 2011-07-20 | Takeda Pharmaceutical Company Limited | Amorphous (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole as anti-ulcer agent |
| US20110189271A1 (en) * | 2010-02-02 | 2011-08-04 | Vishal Lad | Pharmaceutical formulations of acid-labile drugs |
| WO2011138797A2 (en) | 2010-05-04 | 2011-11-10 | Cadila Healthcare Limited | Delayed release oral disintegrating pharmaceutical compositions of lansoprazole |
| US8071128B2 (en) | 1996-06-14 | 2011-12-06 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| WO2012001705A2 (en) | 2010-06-29 | 2012-01-05 | Cadila Healthcare Limited | Pharmaceutical compositions of (r)-lansoprazole |
| WO2012027331A1 (en) | 2010-08-27 | 2012-03-01 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| US8173158B2 (en) | 2007-10-12 | 2012-05-08 | Takeda Pharmaceuticals U.S.A., Inc. | Methods of treating gastrointestinal disorders independent of the intake of food |
| WO2012074110A1 (en) | 2010-12-03 | 2012-06-07 | 武田薬品工業株式会社 | Orally disintegrating tablet |
| WO2012091153A2 (en) | 2010-12-27 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Orally disintegrating tablet |
| US8222422B2 (en) | 2008-03-10 | 2012-07-17 | Takeda Pharmaceutical Company Limited | Crystal of benzimidazole compound |
| EP2486910A2 (en) | 2006-10-27 | 2012-08-15 | The Curators Of The University Of Missouri | Multi-chambered apparatus comprising a dispenser head |
| WO2012134828A1 (en) | 2011-03-25 | 2012-10-04 | Takeda Pharmaceuticals U.S.A., Inc. | Methods for treating heartburn and/or preventing gastric bleeding or hemorrhage in patients receiving clopidogrel therapy |
| US8367111B2 (en) | 2002-12-31 | 2013-02-05 | Aptalis Pharmatech, Inc. | Extended release dosage forms of propranolol hydrochloride |
| US8394409B2 (en) | 2004-07-01 | 2013-03-12 | Intellipharmaceutics Corp. | Controlled extended drug release technology |
| WO2013081177A1 (en) | 2011-11-30 | 2013-06-06 | Takeda Pharmaceutical Company Limited | Dry coated tablet |
| US8461187B2 (en) | 2004-06-16 | 2013-06-11 | Takeda Pharmaceuticals U.S.A., Inc. | Multiple PPI dosage form |
| WO2013088109A1 (en) | 2011-12-16 | 2013-06-20 | Oxagen Limited | Combination of crth2 antagonist and a proton pump inhibitor for the treatment of eosinophilic esophagitis |
| WO2013108068A1 (en) | 2012-01-21 | 2013-07-25 | Jubilant Life Sciences Limited | Process for the preparation of 2-pyridinylmethylsulfinyl benzimidazoles, their analogs and optically active enantiomers |
| US8580313B2 (en) | 2009-12-02 | 2013-11-12 | Aptalis Pharma Limited | Fexofenadine microcapsules and compositions containing them |
| US8747895B2 (en) | 2004-09-13 | 2014-06-10 | Aptalis Pharmatech, Inc. | Orally disintegrating tablets of atomoxetine |
| US8778922B2 (en) | 2009-01-08 | 2014-07-15 | Lipocine Inc. | Steroidal compositions |
| WO2014113377A1 (en) | 2013-01-15 | 2014-07-24 | Ironwood Pharmaceuticals, Inc. | Gastro-retentive sustained-release oral dosage form of a bile acid sequestrant |
| US8815916B2 (en) | 2004-05-25 | 2014-08-26 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| USRE45198E1 (en) | 1996-01-04 | 2014-10-14 | The Curators Of The University Of Missouri | Omeprazole solution and method for using same |
| WO2014189034A1 (en) | 2013-05-21 | 2014-11-27 | 武田薬品工業株式会社 | Orally disintegrable tablet |
| US8906940B2 (en) | 2004-05-25 | 2014-12-09 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US8993599B2 (en) | 2003-07-18 | 2015-03-31 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US9034858B2 (en) | 2010-11-30 | 2015-05-19 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9040086B2 (en) | 2001-10-04 | 2015-05-26 | Aptalis Pharmatech, Inc. | Timed, sustained release systems for propranolol |
| US9078827B2 (en) | 2006-05-12 | 2015-07-14 | Isa Odidi | Pharmaceutical composition having reduced abuse potential |
| US9161918B2 (en) | 2005-05-02 | 2015-10-20 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US9358241B2 (en) | 2010-11-30 | 2016-06-07 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| WO2016126625A1 (en) | 2015-02-03 | 2016-08-11 | Ironwood Pharmaceuticals, Inc. | Methods of treating upper gastrointestinal disorders in ppi refractory gerd |
| US9498485B2 (en) | 2014-08-28 | 2016-11-22 | Lipocine Inc. | Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters |
| US9561188B2 (en) | 2006-04-03 | 2017-02-07 | Intellipharmaceutics Corporation | Controlled release delivery device comprising an organosol coat |
| CN107365300A (en) * | 2017-07-26 | 2017-11-21 | 桂林华信制药有限公司 | A kind of method for effectively removing impurity in Lansoprazole crude product |
| US9884014B2 (en) | 2004-10-12 | 2018-02-06 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| US10064828B1 (en) | 2005-12-23 | 2018-09-04 | Intellipharmaceutics Corp. | Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems |
| US10076494B2 (en) | 2016-06-16 | 2018-09-18 | Dexcel Pharma Technologies Ltd. | Stable orally disintegrating pharmaceutical compositions |
| US10471017B2 (en) | 2004-10-21 | 2019-11-12 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions with gastrosoluble pore-formers |
| US10561615B2 (en) | 2010-12-10 | 2020-02-18 | Lipocine Inc. | Testosterone undecanoate compositions |
| US10624858B2 (en) | 2004-08-23 | 2020-04-21 | Intellipharmaceutics Corp | Controlled release composition using transition coating, and method of preparing same |
| US10736855B2 (en) | 2016-02-25 | 2020-08-11 | Dexcel Pharma Technologies Ltd. | Compositions comprising proton pump inhibitors |
| US11077055B2 (en) | 2015-04-29 | 2021-08-03 | Dexcel Pharma Technologies Ltd. | Orally disintegrating compositions |
| US11273145B2 (en) | 2014-02-25 | 2022-03-15 | Muslim D. Shahid | Compositions and methods for the treatment of acid-related gastrointestinal disorders containing a dithiolane compound and a gastric acid secretion inhibitor |
| US11433083B2 (en) | 2010-11-30 | 2022-09-06 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US11559530B2 (en) | 2016-11-28 | 2023-01-24 | Lipocine Inc. | Oral testosterone undecanoate therapy |
| US11707467B2 (en) | 2014-08-28 | 2023-07-25 | Lipocine Inc. | (17-ß)-3-oxoandrost-4-en-17YL tridecanoate compositions and methods of their preparation and use |
| WO2024075017A1 (en) | 2022-10-04 | 2024-04-11 | Zabirnyk Arsenii | Inhibition of aortic valve calcification |
Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0174717B1 (en) | 1984-07-06 | 1992-01-22 | FISONS plc | Benzimidazoles, and their production formulation and use as gastric acid secretion inhibitors |
| US5433959A (en) | 1986-02-13 | 1995-07-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| US6749864B2 (en) * | 1986-02-13 | 2004-06-15 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| CA1327010C (en) * | 1986-02-13 | 1994-02-15 | Tadashi Makino | Stabilized solid pharmaceutical composition containing antiulcer benzimidazole compound and its production |
| CA1276017C (en) * | 1986-02-13 | 1990-11-06 | Takeda Chemical Industries, Ltd. | Sulfenamide derivatives and their production |
| JPH03504497A (en) * | 1988-05-25 | 1991-10-03 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | New fluoroalkoxy compound |
| US5223515A (en) * | 1988-08-18 | 1993-06-29 | Takeda Chemical Industries, Ltd. | Injectable solution containing a pyridyl methylsulfinylbenzimidazole |
| JP2536173B2 (en) * | 1988-08-18 | 1996-09-18 | 武田薬品工業株式会社 | Injection |
| AT391693B (en) * | 1988-11-15 | 1990-11-12 | Cl Pharma | METHOD FOR PRODUCING 3-5-DIMETHYL-4METHOXYPYRIDINE DERIVATIVES AND NEW INTERMEDIATE PRODUCT THEREFOR |
| ATE114114T1 (en) * | 1989-02-10 | 1994-12-15 | Takeda Chemical Industries Ltd | USE OF BENZIMIDAZOLE DERIVATIVES AS ANTIBACTERIAL AGENTS. |
| WO1993006097A1 (en) * | 1991-09-20 | 1993-04-01 | Merck & Co., Inc. | Novel process for the preparation of anti-ulcer agents |
| ES2036948B1 (en) * | 1991-11-21 | 1994-09-01 | Genesis Para La Investigacion | PROCEDURE FOR OBTAINING COMPOUNDS DERIVED FROM PIRIDINE. |
| ES2060541B1 (en) * | 1993-02-26 | 1995-11-16 | Vinas Lab | NEW PROCEDURE FOR THE SYNTHESIS OF A DERIVATIVE OF 2- (2-PIRIDILMETILSUFINIL) BENCIMIDAZOLE, AND NEW INTERMEDIATE PRODUCTS OBTAINED WITH THE SAME. |
| ES2063705B1 (en) * | 1993-06-14 | 1995-07-16 | S A L V A T Lab Sa | INTERMEDIATE FOR THE SYNTHESIS OF LANSOPRAZOLE AND ITS PROCEDURE FOR OBTAINING. |
| CN1048980C (en) * | 1994-03-29 | 2000-02-02 | 广东汕头鮀滨化学药业总公司 | Preparation of pyridine derivative and application thereof |
| SE9402431D0 (en) * | 1994-07-08 | 1994-07-08 | Astra Ab | New tablet formulation |
| GB9423968D0 (en) * | 1994-11-28 | 1995-01-11 | Astra Ab | Resolution |
| SE9500422D0 (en) * | 1995-02-06 | 1995-02-06 | Astra Ab | New oral pharmaceutical dosage forms |
| US5708017A (en) * | 1995-04-04 | 1998-01-13 | Merck & Co., Inc. | Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors |
| HRP960232A2 (en) * | 1995-07-03 | 1998-02-28 | Astra Ab | A process for the optical purification of compounds |
| US6489346B1 (en) * | 1996-01-04 | 2002-12-03 | The Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
| US6699885B2 (en) * | 1996-01-04 | 2004-03-02 | The Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and methods of using same |
| US6645988B2 (en) * | 1996-01-04 | 2003-11-11 | Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
| SE9600070D0 (en) | 1996-01-08 | 1996-01-08 | Astra Ab | New oral pharmaceutical dosage forms |
| US6380222B2 (en) | 1996-10-11 | 2002-04-30 | Astrazeneca Ab | Use of an H+, K+-atpase inhibitor in the treatment of nasal polyps |
| TW385306B (en) * | 1996-11-14 | 2000-03-21 | Takeda Chemical Industries Ltd | Method for producing crystals of benzimidazole derivatives |
| AU6551198A (en) * | 1997-05-30 | 1998-12-30 | Dr. Reddy's Research Foundation | Novel benzimidazole derivatives as antiulcer agents, process for their preparation and pharmaceutical compositions containing them |
| WO1999004816A1 (en) | 1997-07-25 | 1999-02-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Proton pump inhibitor in therapeutic combination with antibacterial substances |
| SE9704870D0 (en) * | 1997-12-22 | 1997-12-22 | Astra Ab | New pharmaceutical formulation I |
| KR101032289B1 (en) | 1998-05-18 | 2011-05-06 | 다케다 야쿠힌 고교 가부시키가이샤 | Fine granules |
| IE990506A1 (en) * | 1998-06-26 | 2000-11-15 | Russinsky Ltd | Pyridine Building Blocks |
| SI20019A (en) * | 1998-07-13 | 2000-02-29 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | An improved process for synthesis of 5-methoxy-2-/(4-methoxy-3,5-dimethyl-2-pyridyl)methyl/ sulphynyl-1h-benzimidazol |
| US7041313B1 (en) | 1998-08-12 | 2006-05-09 | Altana Pharma Ag | Oral administration form for pyridin-2-ylmethylsulfinyl-1H-benzimidazoles |
| DE19843413C1 (en) * | 1998-08-18 | 2000-03-30 | Byk Gulden Lomberg Chem Fab | New salt form of pantoprazole |
| TWI243672B (en) | 1999-06-01 | 2005-11-21 | Astrazeneca Ab | New use of compounds as antibacterial agents |
| ATE300285T1 (en) | 1999-06-07 | 2005-08-15 | Altana Pharma Ag | NEW PREPARATION AND PHARMACEUTICAL FORM CONTAINING AN ACID LABEL PROTON PUMP INHIBITOR |
| SE9903831D0 (en) * | 1999-10-22 | 1999-10-22 | Astra Ab | Formulation of substituted benzimidazoles |
| US7732404B2 (en) | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
| SE0000774D0 (en) | 2000-03-08 | 2000-03-08 | Astrazeneca Ab | New formulation |
| CA2775616C (en) | 2000-08-04 | 2013-09-17 | Takeda Pharmaceutical Company Limited | Salts of benzimidazole compound and application thereof |
| AU2002234545A1 (en) | 2000-12-07 | 2002-06-18 | Byk Gulden Lomberg Chemische Fabrik G.M.B.H. | Pharmaceutical preparation in the form of a suspension comprising an acid-labileactive ingredient |
| WO2002045686A2 (en) | 2000-12-07 | 2002-06-13 | Altana Pharma Ag | Pharmaceutical paste comprising an acid-labile active ingredient |
| PT1341528E (en) | 2000-12-07 | 2012-03-20 | Nycomed Gmbh | Rapidly disintegrating tablet comprising an acid-labile active ingredient |
| SE0101379D0 (en) | 2001-04-18 | 2001-04-18 | Diabact Ab | Composition that inhibits gastric acid secretion |
| US8206741B2 (en) | 2001-06-01 | 2012-06-26 | Pozen Inc. | Pharmaceutical compositions for the coordinated delivery of NSAIDs |
| SE0102993D0 (en) | 2001-09-07 | 2001-09-07 | Astrazeneca Ab | New self emulsifying drug delivery system |
| US8101209B2 (en) | 2001-10-09 | 2012-01-24 | Flamel Technologies | Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles |
| IL164221A0 (en) | 2002-04-09 | 2005-12-18 | Flamel Tech Sa | Oral pharmaceutical formulation in the form of aqueous suspension of microcapsules for modified release of amoxicillim |
| IL164222A0 (en) | 2002-04-09 | 2005-12-18 | Flamel Tech Sa | Oral pharmaceutical formulation in the form of aqueous suspension for modified release of active principle(s) |
| TW200410955A (en) | 2002-07-29 | 2004-07-01 | Altana Pharma Ag | Novel salt of (S)-PANTOPRAZOLE |
| JP4746318B2 (en) | 2002-08-30 | 2011-08-10 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | A pharmaceutical composition for the treatment of allergic rhinitis comprising a combination of ciclesonide and an antihistamine |
| SE0203065D0 (en) | 2002-10-16 | 2002-10-16 | Diabact Ab | Gastric acid secretion inhibiting composition |
| DE10254167A1 (en) | 2002-11-20 | 2004-06-09 | Icon Genetics Ag | Process for the control of cellular processes in plants |
| US7301030B2 (en) | 2002-12-06 | 2007-11-27 | Nycomed Gmbh | Process for preparing (S)-pantoprazole |
| WO2004052882A1 (en) | 2002-12-06 | 2004-06-24 | Altana Pharma Ag | Process for preparing optically pure active compounds |
| US8449911B2 (en) | 2003-03-12 | 2013-05-28 | Takeda Pharmaceutical Company Limited | Drug composition having active ingredient adhered at high concentration to spherical core |
| PE20050150A1 (en) | 2003-05-08 | 2005-03-22 | Altana Pharma Ag | A DOSAGE FORM CONTAINING (S) -PANTOPRAZOLE AS AN ACTIVE INGREDIENT |
| CL2004000983A1 (en) | 2003-05-08 | 2005-03-04 | Altana Pharma Ag | ORAL PHARMACEUTICAL COMPOSITION IN THE FORM OF A TABLET THAT INCLUDES DIHYDRATED MAGNETIC PANTOPRAZOL, WHERE THE TABLET FORM IS COMPOSED BY A NUCLEUS, A MIDDLE COAT AND AN OUTER LAYER; AND USE OF PHARMACEUTICAL COMPOSITION IN ULCERAS AND |
| TWI372066B (en) | 2003-10-01 | 2012-09-11 | Wyeth Corp | Pantoprazole multiparticulate formulations |
| CA2561700A1 (en) * | 2004-04-16 | 2005-12-15 | Santarus, Inc. | Combination of proton pump inhibitor, buffering agent, and prokinetic agent |
| CN1946722A (en) * | 2004-04-28 | 2007-04-11 | 奥坦纳医药公司 | Dialkoxy-imidazopyridines derivatives |
| US20060105038A1 (en) * | 2004-11-12 | 2006-05-18 | Eurand Pharmaceuticals Limited | Taste-masked pharmaceutical compositions prepared by coacervation |
| EP1814591A4 (en) | 2004-11-22 | 2009-04-22 | Anadis Ltd | Bioactive compositions |
| EP1681056A1 (en) | 2005-01-14 | 2006-07-19 | Krka Tovarna Zdravil, D.D., Novo Mesto | Process for preparing lansoprazole |
| US7803817B2 (en) | 2005-05-11 | 2010-09-28 | Vecta, Ltd. | Composition and methods for inhibiting gastric acid secretion |
| US7981908B2 (en) | 2005-05-11 | 2011-07-19 | Vecta, Ltd. | Compositions and methods for inhibiting gastric acid secretion |
| US7601737B2 (en) | 2005-07-26 | 2009-10-13 | Nycomed Gmbh | Isotopically substituted proton pump inhibitors |
| EP1967211A4 (en) | 2005-12-28 | 2009-12-30 | Takeda Pharmaceutical | Method of producing solid preparation disintegrating in the oral cavity |
| PT2003130E (en) * | 2006-03-10 | 2012-01-10 | Arigen Pharmaceuticals Inc | Novel pyridine derivative having anti-helicobacter pylori activity |
| JP5474541B2 (en) | 2006-07-25 | 2014-04-16 | ベクタ・リミテッド | Compositions and methods for inhibiting gastric acid secretion using PPI in combination with small dicarboxylic acid derivatives |
| TW200840574A (en) * | 2007-04-02 | 2008-10-16 | Univ Nat Taiwan | The pharmaceutical component for treating hearing loss disease |
| EP2344139A1 (en) | 2008-09-09 | 2011-07-20 | AstraZeneca AB | Method for delivering a pharmaceutical composition to patient in need thereof |
| JP2012531409A (en) | 2009-06-25 | 2012-12-10 | アストラゼネカ・アクチエボラーグ | Methods for treating patients at risk of developing NSAID-related ulcers |
| WO2011080502A2 (en) | 2009-12-29 | 2011-07-07 | Orexo Ab | New pharmaceutical dosage form for the treatment of gastric acid-related disorders |
| WO2011080501A2 (en) | 2009-12-29 | 2011-07-07 | Orexo Ab | New pharmaceutical dosage form for the treatment of gastric acid-related disorders |
| WO2011080500A2 (en) | 2009-12-29 | 2011-07-07 | Orexo Ab | New pharmaceutical dosage form for the treatment of gastric acid-related disorders |
| TW201127375A (en) * | 2010-01-08 | 2011-08-16 | Eurand Inc | Taste masked topiramate composition and an orally disintegrating tablet comprising the same |
| EP2601947A1 (en) | 2011-12-05 | 2013-06-12 | Abo Bakr Mohammed Ali Al-Mehdar | Fixed-dose combination for treatment of helicobacter pylori associated diseases |
| EA028049B1 (en) | 2011-12-28 | 2017-10-31 | Поузен Инк. | Improved compositions and methods for delivery of omeprazole plus acetylsalicylic acid |
| CN114163419A (en) * | 2021-12-24 | 2022-03-11 | 辰欣药业股份有限公司 | Preparation method of lansoprazole |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4045563A (en) * | 1974-05-16 | 1977-08-30 | Ab Hassle | Substituted 2-[pyridylalkylenesulfinyl]-benzimidazoles with gastric acid secretion inhibiting effects |
| US4255431A (en) * | 1978-04-14 | 1981-03-10 | Aktiebolaget Hassle | Gastric acid secretion inhibiting substituted 2-(2-benzimidazolyl)-pyridines, pharmaceutical preparations containing same, and method for inhibiting gastric acid secretion |
| EP0045200A1 (en) * | 1980-07-28 | 1982-02-03 | The Upjohn Company | Benzimidazoles and their pharmaceutical use |
| GB2134523A (en) * | 1983-02-11 | 1984-08-15 | Haessle Ab | Novel pharmacologically active compounds |
| US4472409A (en) * | 1981-11-05 | 1984-09-18 | Byk Gulden Lomberg Chemische Fabrik Gesellschaft Mit Beschrankter Haftung | 2-Pyridylmethyl thio(sulfinyl)benzimidazoles with gastric acid secretion inhibiting effects |
| US4575554A (en) * | 1983-12-05 | 1986-03-11 | The Upjohn Company | Substituted 2-pyridylmethylthio- and sulfinyl-benzimidazoles as gastric antisecretory agents |
| EP0074341B1 (en) * | 1981-08-13 | 1986-03-26 | Aktiebolaget Hässle | Novel pharmaceutical compositions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU195220B (en) * | 1983-05-03 | 1988-04-28 | Byk Gulden Lomberg Chem Fqb | Process for production of new fluor-alkoxi-benzimidasole-derivatives and medical compositions containig them |
| IL75400A (en) * | 1984-06-16 | 1988-10-31 | Byk Gulden Lomberg Chem Fab | Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same |
| GB8417171D0 (en) * | 1984-07-05 | 1984-08-08 | Beecham Group Plc | Compounds |
| SE8404065D0 (en) * | 1984-08-10 | 1984-08-10 | Haessle Ab | NOVEL BIOLOGICALLY ACTIVE COMPOUNDS |
-
1984
- 1984-08-16 JP JP59171069A patent/JPS6150978A/en active Granted
-
1985
- 1985-07-29 US US06/760,568 patent/US4628098A/en not_active Expired - Lifetime
- 1985-07-31 DE DE19975017C patent/DE19975017I2/en active Active
- 1985-07-31 DE DE19975020C patent/DE19975020I2/en active Active
- 1985-07-31 EP EP19850305458 patent/EP0174726B1/en not_active Expired
- 1985-07-31 DE DE8585305458T patent/DE3569736D1/en not_active Expired
- 1985-08-06 DK DK356485A patent/DK171340B1/en active Protection Beyond IP Right Term
- 1985-08-07 AU AU45895/85A patent/AU570130B2/en not_active Expired
- 1985-08-09 IE IE197685A patent/IE58363B1/en not_active IP Right Cessation
- 1985-08-13 ZA ZA856117A patent/ZA856117B/en unknown
- 1985-08-13 GR GR851981A patent/GR851981B/el unknown
- 1985-08-13 PH PH32628A patent/PH20946A/en unknown
- 1985-08-14 KR KR1019850005863A patent/KR920002128B1/en not_active IP Right Cessation
- 1985-08-14 CA CA000488662A patent/CA1255314A/en not_active Expired
- 1985-08-14 UA UA3947161A patent/UA7140A1/en unknown
- 1985-08-14 ES ES546152A patent/ES8607288A1/en not_active Expired
- 1985-08-14 SU SU3947161A patent/SU1507211A3/en active
- 1985-08-15 HU HU853151A patent/HU195210B/en unknown
- 1985-08-15 NO NO853226A patent/NO163131C/en not_active IP Right Cessation
-
1986
- 1986-12-02 US US06/937,193 patent/US4689333A/en not_active Expired - Lifetime
-
1991
- 1991-12-04 SG SG1032/91A patent/SG103291G/en unknown
-
1992
- 1992-01-16 HK HK47/92A patent/HK4792A/en not_active IP Right Cessation
- 1992-06-19 MX MX9203043A patent/MX9203043A/en unknown
-
1993
- 1993-03-11 GE GEAP1993601A patent/GEP19960313B/en unknown
- 1993-06-29 NL NL930109C patent/NL930109I2/en unknown
-
1994
- 1994-02-11 BG BG98459A patent/BG60415B2/en unknown
-
1995
- 1995-03-31 NO NO1995002C patent/NO1995002I1/en unknown
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4045563A (en) * | 1974-05-16 | 1977-08-30 | Ab Hassle | Substituted 2-[pyridylalkylenesulfinyl]-benzimidazoles with gastric acid secretion inhibiting effects |
| US4255431A (en) * | 1978-04-14 | 1981-03-10 | Aktiebolaget Hassle | Gastric acid secretion inhibiting substituted 2-(2-benzimidazolyl)-pyridines, pharmaceutical preparations containing same, and method for inhibiting gastric acid secretion |
| EP0005129B1 (en) * | 1978-04-14 | 1981-04-29 | Aktiebolaget Hässle | Substituted pyridylsulfinylbenzimidazoles having gastric acid secretion properties, pharmaceutical preparations containing same, and intermediates for their preparation |
| EP0045200A1 (en) * | 1980-07-28 | 1982-02-03 | The Upjohn Company | Benzimidazoles and their pharmaceutical use |
| EP0074341B1 (en) * | 1981-08-13 | 1986-03-26 | Aktiebolaget Hässle | Novel pharmaceutical compositions |
| US4472409A (en) * | 1981-11-05 | 1984-09-18 | Byk Gulden Lomberg Chemische Fabrik Gesellschaft Mit Beschrankter Haftung | 2-Pyridylmethyl thio(sulfinyl)benzimidazoles with gastric acid secretion inhibiting effects |
| GB2134523A (en) * | 1983-02-11 | 1984-08-15 | Haessle Ab | Novel pharmacologically active compounds |
| US4575554A (en) * | 1983-12-05 | 1986-03-11 | The Upjohn Company | Substituted 2-pyridylmethylthio- and sulfinyl-benzimidazoles as gastric antisecretory agents |
Cited By (298)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5578732A (en) * | 1987-08-04 | 1996-11-26 | Takeda Chemical Industries, Ltd. | Production of 2-(2-pyridylmethylsulfinyl) benzimidazole compounds by selective oxidation in the presence of a vanadium catalyst |
| US5008278A (en) * | 1988-12-22 | 1991-04-16 | Aktiebolaget Hassle | Therapeutically active compound and a process for its preparation |
| US5025024A (en) * | 1988-12-22 | 1991-06-18 | Aktiebolaget Hassle | Therapeutically active fluoro-substituted compound |
| LT3980B (en) | 1988-12-22 | 1996-06-25 | Haessle Ab | New therapeutically active compound and a process for its preparation |
| LT3981B (en) | 1988-12-22 | 1996-06-25 | Haessle Ab | Therapeutically active substituted benzimidazole and process for its preparation |
| US5441968A (en) * | 1989-12-20 | 1995-08-15 | Aktiebolaget Hassle | Therapeutically active fluoro substituted benzimidazoles |
| US5049674A (en) * | 1989-12-20 | 1991-09-17 | Aktiebolaget Hassle | Therapeutically active fluoro substituted benzimidazoles |
| US4965269A (en) * | 1989-12-20 | 1990-10-23 | Ab Hassle | Therapeutically active chloro substituted benzimidazoles |
| EP0481764A1 (en) | 1990-10-17 | 1992-04-22 | Takeda Chemical Industries, Ltd. | Pyridine derivatives, their production and use |
| US5312824A (en) * | 1990-10-17 | 1994-05-17 | Takeda Chemical Industries, Ltd. | Certain 2-[(4-difluoromethoxy-2-pyridyl)-methylthio or methylsulfinyl-5-benzimidazoles useful for treating peptic ulcers |
| EP0514008A1 (en) | 1991-04-19 | 1992-11-19 | Takeda Chemical Industries, Ltd. | Pharmaceutical preparations based on gastrointestinal mucosa-adherent matrixes or coatings |
| US5389664A (en) * | 1992-07-08 | 1995-02-14 | Monsanto Company | Alleviating stomach ulcers in swine |
| US5589491A (en) * | 1992-07-28 | 1996-12-31 | Astra Aktiebolag | Injection and injection kit containing omeprazole and its analogs |
| US5587389A (en) * | 1993-02-17 | 1996-12-24 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Substituted heteroarylaklylthiopyridines for controlling helicobacter bacteria |
| EP0649655A1 (en) | 1993-10-15 | 1995-04-26 | Takeda Chemical Industries, Ltd. | Injectable solutions containing anti-ulcer benzimidazoles and amides |
| US5536735A (en) * | 1993-10-15 | 1996-07-16 | Takeda Chemical Industries, Ltd. | Pharmaceutical composition |
| US5470983A (en) * | 1993-11-04 | 1995-11-28 | Torcan Chemical Ltd. | Preparation of omeprazole and lansoprazole, and intermediates useful therein |
| US5502195A (en) * | 1993-11-04 | 1996-03-26 | Slemon; Clarke | Sulfoxide-carboxylate intermediates of omeprazole and lansoprazole |
| US5374730A (en) * | 1993-11-04 | 1994-12-20 | Torcan Chemical Ltd. | Preparation of omeprazole and lansoprazole |
| US20040234594A1 (en) * | 1995-02-09 | 2004-11-25 | Per Johan Lundberg | Pharmaceutical formulation and process |
| US6013281A (en) * | 1995-02-09 | 2000-01-11 | Astra Aktiebolag | Method of making a pharmaceutical dosage form comprising a proton pump inhibitor |
| US5824339A (en) * | 1995-09-08 | 1998-10-20 | Takeda Chemical Industries, Ltd | Effervescent composition and its production |
| US6159499A (en) * | 1995-09-21 | 2000-12-12 | Pharma Pass Llc | Composition containing an acid-labile benzimidazole and process for its preparation |
| US5958955A (en) * | 1995-12-15 | 1999-09-28 | Astra Aktiebolag | Method for the synthesis of a benzimidazole compound |
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| US8071128B2 (en) | 1996-06-14 | 2011-12-06 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| US8357396B2 (en) | 1996-06-14 | 2013-01-22 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| US8956650B2 (en) | 1996-06-14 | 2015-02-17 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| US8945618B2 (en) | 1996-06-14 | 2015-02-03 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| US20020128293A1 (en) * | 1998-05-28 | 2002-09-12 | Ashok Rampal | Stable oral pharmaceutical composition containing omeprazole |
| US20040077688A1 (en) * | 1998-07-22 | 2004-04-22 | Sepracor Inc. | Hydroxylansoprazole methods |
| US7098224B2 (en) | 1998-07-22 | 2006-08-29 | Sepracor Inc. | Hydroxylansoprazole methods |
| US6559167B1 (en) | 1998-08-10 | 2003-05-06 | Regents Of The University Of California | Prodrugs of proton pump inhibitors |
| US6093734A (en) * | 1998-08-10 | 2000-07-25 | Partnership Of Michael E. Garst, George Sachs, And Jai Moo Shin | Prodrugs of proton pump inhibitors |
| BG64870B1 (en) * | 1998-08-10 | 2006-07-31 | Partnership Of Michael E. Garst, George Sachs Andjai Moo Shin | Substitutes of inhibitor medicaments with proton pump |
| US6180652B1 (en) | 1998-11-16 | 2001-01-30 | Eisai Co., Ltd. | Sulfoxide compounds and acetone complexes, and a process for producing the same |
| CN1317275C (en) * | 1998-11-16 | 2007-05-23 | 卫材R&D管理有限公司 | Sulfoxide compound and complex of acetone, and production method thereof |
| US6545024B1 (en) | 1998-11-16 | 2003-04-08 | Eisai Co., Ltd. | Sulfoxide compounds and acetone complexes, and a process for producing the same |
| US20040224989A1 (en) * | 1999-01-29 | 2004-11-11 | Barberich Timothy J. | S-lansoprazole compositions and methods |
| US20060142346A1 (en) * | 1999-01-29 | 2006-06-29 | Barberich Timothy J | S-lansoprazole compositions and methods |
| US6852739B1 (en) * | 1999-02-26 | 2005-02-08 | Nitromed Inc. | Methods using proton pump inhibitors and nitric oxide donors |
| US20040266828A1 (en) * | 1999-02-26 | 2004-12-30 | Nitromed, Inc. | Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use |
| US7332505B2 (en) | 1999-02-26 | 2008-02-19 | Nitromed, Inc. | Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use |
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| EP1977751A1 (en) | 1999-06-17 | 2008-10-08 | Takeda Pharmaceutical Company Limited | Use of crystalline (r)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1h-benzimidazole for manufacturing pharmaceutical compositions |
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| US7189744B2 (en) | 1999-06-30 | 2007-03-13 | Takeda Pharmaceutical Company, Limited | Crystals of benzimidazole compounds |
| US6245913B1 (en) | 1999-06-30 | 2001-06-12 | Wockhardt Europe Limited | Synthetic procedure for 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-IH-benzimidazole hydrochloride and its conversion to omeprazole |
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| US6228400B1 (en) | 1999-09-28 | 2001-05-08 | Carlsbad Technology, Inc. | Orally administered pharmaceutical formulations of benzimidazole derivatives and the method of preparing the same |
| KR100359256B1 (en) * | 1999-10-06 | 2002-11-04 | 한미약품공업 주식회사 | Improved method of preparing lansoprazole |
| US20030180352A1 (en) * | 1999-11-23 | 2003-09-25 | Patel Mahesh V. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| US20060034937A1 (en) * | 1999-11-23 | 2006-02-16 | Mahesh Patel | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| KR100757346B1 (en) * | 2000-04-14 | 2007-09-11 | 에스티브 퀴미카 에스.에이. | Method for obtaining derivatives of [[pyridil substitutedmethyl]thio]benzimidazol |
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| US7569696B2 (en) | 2000-05-15 | 2009-08-04 | Takeda Pharmaceutical Company Limited | Process for producing crystal |
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| US20070004779A1 (en) * | 2000-05-15 | 2007-01-04 | Hideo Hashimoto | Process for producing crystal |
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| US6544556B1 (en) | 2000-09-11 | 2003-04-08 | Andrx Corporation | Pharmaceutical formulations containing a non-steroidal antiinflammatory drug and a proton pump inhibitor |
| US6869615B2 (en) | 2000-09-11 | 2005-03-22 | Andrx Labs Llc | Pharmaceutical formulations containing a non-steroidal antiinflammatory drug and a proton pump inhibitor |
| US20030211147A1 (en) * | 2000-09-29 | 2003-11-13 | Cullen Daniel J. | Proton pump inhibitor formulation |
| EP2345650A1 (en) | 2000-12-01 | 2011-07-20 | Takeda Pharmaceutical Company Limited | Amorphous (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole as anti-ulcer agent |
| WO2002074766A1 (en) * | 2001-02-21 | 2002-09-26 | Chemtech Research Incorporation | Method of preparing lansoprazole and its intermediate |
| EP2301556A1 (en) | 2001-03-27 | 2011-03-30 | Pro-Pharmaceuticals, Inc. | Co-Administration of a Polysaccharide with a Chemotherapeutic Agent for the Treatment of Cancer |
| US6884810B2 (en) * | 2001-09-18 | 2005-04-26 | Zeria Pharmaceutical Co., Ltd. | Benzimidazole derivatives |
| US20030236411A1 (en) * | 2001-09-18 | 2003-12-25 | Masaaki Nagasawa | Benzimidazole derivatives |
| US20040248941A1 (en) * | 2001-09-25 | 2004-12-09 | Keiji Kamiyama | Benzimidazone compound, process for producing the same, and use thereof |
| US9040086B2 (en) | 2001-10-04 | 2015-05-26 | Aptalis Pharmatech, Inc. | Timed, sustained release systems for propranolol |
| US9358214B2 (en) | 2001-10-04 | 2016-06-07 | Adare Pharmaceuticals, Inc. | Timed, sustained release systems for propranolol |
| EP2258351A2 (en) | 2001-10-17 | 2010-12-08 | Takeda Pharmaceutical Company Limited | Granules containing lansoprazole in large amount |
| US20050049282A1 (en) * | 2001-12-18 | 2005-03-03 | Astrazeneca Ab | Process |
| US20030228363A1 (en) * | 2002-06-07 | 2003-12-11 | Patel Mahendra R. | Stabilized pharmaceutical compositons containing benzimidazole compounds |
| US20030236285A1 (en) * | 2002-06-07 | 2003-12-25 | Patel Mahendra R. | Stabilized pharmaceutical compositions containing benzimidazole compounds |
| US20040041229A1 (en) * | 2002-06-18 | 2004-03-04 | Chol Young-Chul | Power semiconductor device having high breakdown voltage, low on-resistance, and small switching loss and method of forming the same |
| US6897227B2 (en) | 2002-07-19 | 2005-05-24 | Winston Pharmaceuticals, Inc. | Prodrugs of proton pump inhibitors |
| US20050143423A1 (en) * | 2002-07-19 | 2005-06-30 | Michael Garst | Prodrugs of proton pump inhibitors background of the invention |
| US20040102484A1 (en) * | 2002-07-19 | 2004-05-27 | Michael Garst | Prodrugs of proton pump inhibitors |
| US20050182101A1 (en) * | 2002-07-19 | 2005-08-18 | Michael Garst | Prodrugs of proton pump inhibitors |
| US7211590B2 (en) | 2002-08-01 | 2007-05-01 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| US20070179150A1 (en) * | 2002-08-01 | 2007-08-02 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| US20040024014A1 (en) * | 2002-08-01 | 2004-02-05 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| US7060837B2 (en) | 2002-08-21 | 2006-06-13 | Teva Pharmaceutical Industries Ltd. | Method for the purification of lansoprazole |
| US20050165061A1 (en) * | 2002-08-21 | 2005-07-28 | Teva Pharmaceuticals Industries Ltd. | Method for the purification of lansoprazole |
| US20050165059A1 (en) * | 2002-08-21 | 2005-07-28 | Teva Pharmaceutical Industries Ltd. | Method for the purification of lansoprazole |
| US20050165060A1 (en) * | 2002-08-21 | 2005-07-28 | Teva Pharmaceutical Industries Ltd. | Method for the purification of lansoprazole |
| US7622588B2 (en) | 2002-08-21 | 2009-11-24 | Teva Pharmaceutical Industries Ltd. | Method for the purification of lansoprazole |
| US7022859B2 (en) | 2002-08-21 | 2006-04-04 | Teva Pharmaceutical Industries Ltd. | Method for the purification of lansoprazole |
| US6909004B2 (en) | 2002-08-21 | 2005-06-21 | Teva Pharmaceutical Industries Ltd. | Method for the purification of lansoprazole |
| US9265730B2 (en) | 2002-10-16 | 2016-02-23 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| EP2596791A1 (en) | 2002-10-16 | 2013-05-29 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| US8697097B2 (en) | 2002-10-16 | 2014-04-15 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| US8697094B2 (en) | 2002-10-16 | 2014-04-15 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| EP2283827A1 (en) | 2002-10-16 | 2011-02-16 | Takeda Pharmaceutical Company Limited | Controlled release preparation |
| US20110020410A1 (en) * | 2002-10-16 | 2011-01-27 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| EP2596792A1 (en) | 2002-10-16 | 2013-05-29 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| US20060057195A1 (en) * | 2002-10-16 | 2006-03-16 | Takeda Pharmaceutical Company Limited | Stable solid preparations |
| EP2277510A2 (en) | 2002-10-16 | 2011-01-26 | Takeda Pharmaceutical Company Limited | Controlled release preparation |
| US20040215021A1 (en) * | 2002-11-18 | 2004-10-28 | Anita Liberman | Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| US7683080B2 (en) | 2002-11-18 | 2010-03-23 | Teva Pharmaceutical Industries Ltd. | Stable iansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| EP1743893A1 (en) | 2002-11-18 | 2007-01-17 | Teva Pharmaceutical Industries Ltd. | Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| WO2004046135A1 (en) * | 2002-11-18 | 2004-06-03 | Teva Pharmaceutical Industries Ltd. | Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| US20040177804A1 (en) * | 2002-12-19 | 2004-09-16 | Nina Finkelstein | Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates |
| US20080132707A1 (en) * | 2002-12-19 | 2008-06-05 | Teva Pharmaceuticals Usa, Inc. For Barbados. | Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates |
| US7915423B2 (en) | 2002-12-19 | 2011-03-29 | Teva Pharmaceutical Industries, Ltd. | Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates |
| US7507829B2 (en) | 2002-12-19 | 2009-03-24 | Teva Pharmaceuticals Industries, Ltd | Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates |
| US8367111B2 (en) | 2002-12-31 | 2013-02-05 | Aptalis Pharmatech, Inc. | Extended release dosage forms of propranolol hydrochloride |
| US20050020638A1 (en) * | 2003-02-05 | 2005-01-27 | Claude Singer | Method of stabilizing lansoprazole |
| US7678816B2 (en) | 2003-02-05 | 2010-03-16 | Teva Pharmaceutical Industries Ltd. | Method of stabilizing lansoprazole |
| WO2004072061A1 (en) * | 2003-02-05 | 2004-08-26 | Teva Pharmaceutical Industries Ltd. | Method of stabilizing lansoprazole |
| US20050220870A1 (en) * | 2003-02-20 | 2005-10-06 | Bonnie Hepburn | Novel formulation, omeprazole antacid complex-immediate release for rapid and sustained suppression of gastric acid |
| US20040235904A1 (en) * | 2003-03-12 | 2004-11-25 | Nina Finkelstein | Crystalline and amorphous solids of pantoprazole and processes for their preparation |
| US20060173045A1 (en) * | 2003-03-13 | 2006-08-03 | Shouichi Miyawaki | Preventative or remedy for grinding |
| US7608625B2 (en) | 2003-03-13 | 2009-10-27 | Eisai R & D Management Co., Ltd. | Method for treating bruxism and bruxism-related diseases |
| US20050031696A1 (en) * | 2003-04-22 | 2005-02-10 | Dr. Reddy's Laboratories Limited | Oral pharmaceutical formulations of acid-labile active ingredients and process for making same |
| US20050075370A1 (en) * | 2003-06-10 | 2005-04-07 | Viviana Braude | Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole |
| US7683177B2 (en) | 2003-06-10 | 2010-03-23 | Teva Pharmaceutical Industries Ltd | Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole |
| US9636306B2 (en) | 2003-06-26 | 2017-05-02 | Intellipharmaceutics Corp. | Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient |
| US8603520B2 (en) | 2003-06-26 | 2013-12-10 | Intellipharmaceutics Corp. | Oral multi-functional pharmaceutical capsule preparations of proton pump inhibitors |
| US20040265370A1 (en) * | 2003-06-26 | 2004-12-30 | Isa Odidi | Oral multi-functional pharmaceutical capsule preparations of proton pump inhibitors |
| US8802139B2 (en) | 2003-06-26 | 2014-08-12 | Intellipharmaceutics Corp. | Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient |
| US20050038076A1 (en) * | 2003-07-15 | 2005-02-17 | Garst Michael E. | Process for preparing isomerically pure prodrugs of proton pump inhibitors |
| US7294716B2 (en) | 2003-07-15 | 2007-11-13 | Allergan, Inc. | Process for preparing isomerically pure prodrugs of proton pump inhibitors |
| US8993599B2 (en) | 2003-07-18 | 2015-03-31 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US20050232992A1 (en) * | 2003-09-03 | 2005-10-20 | Agi Therapeutics Limited | Proton pump inhibitor formulations, and methods of preparing and using such formulations |
| US20050075371A1 (en) * | 2003-10-03 | 2005-04-07 | Allergan, Inc. | Methods and compositions for the oral administration of prodrugs of proton pump inhibitors |
| US20060241037A1 (en) * | 2003-10-03 | 2006-10-26 | Allergan Inc. | Compositions comprising trefoil factor family peptides and/or mucoadhesives and proton pump ihhibitor prodrugs |
| US20050249806A1 (en) * | 2004-02-10 | 2005-11-10 | Santarus, Inc. | Combination of proton pump inhibitor, buffering agent, and nonsteroidal anti-inflammatory drug |
| US20080160106A1 (en) * | 2004-02-12 | 2008-07-03 | Istituto Superiore De Sanita | Novel Uses for Proton Pump Inhibitors |
| US20070161679A1 (en) * | 2004-02-18 | 2007-07-12 | Allergan, Inc. | Method and compositions for the intravenous administration of compounds related to proton pump inhibitors |
| US20070060621A1 (en) * | 2004-02-18 | 2007-03-15 | Hughes Patrick M | Methods and compositions for the administration of prodrugs of proton pump inhibitors |
| US20050214371A1 (en) * | 2004-03-03 | 2005-09-29 | Simona Di Capua | Stable pharmaceutical composition comprising an acid labile drug |
| US20050214372A1 (en) * | 2004-03-03 | 2005-09-29 | Simona Di Capua | Stable pharmaceutical composition comprising an acid labile drug |
| US8815916B2 (en) | 2004-05-25 | 2014-08-26 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US8906940B2 (en) | 2004-05-25 | 2014-12-09 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US8461187B2 (en) | 2004-06-16 | 2013-06-11 | Takeda Pharmaceuticals U.S.A., Inc. | Multiple PPI dosage form |
| US9889152B2 (en) | 2004-06-16 | 2018-02-13 | Takeda Pharmaceuticals U.S.A., Inc. | Multiple PPI dosage form |
| US9238029B2 (en) | 2004-06-16 | 2016-01-19 | Takeda Pharmaceuticals U.S.A., Inc. | Multiple PPI dosage form |
| US8394409B2 (en) | 2004-07-01 | 2013-03-12 | Intellipharmaceutics Corp. | Controlled extended drug release technology |
| US20060024362A1 (en) * | 2004-07-29 | 2006-02-02 | Pawan Seth | Composition comprising a benzimidazole and process for its manufacture |
| US8968776B2 (en) | 2004-07-29 | 2015-03-03 | Ucb, Inc. | Composition comprising a benzimidazole and process for its manufacture |
| US10624858B2 (en) | 2004-08-23 | 2020-04-21 | Intellipharmaceutics Corp | Controlled release composition using transition coating, and method of preparing same |
| WO2006030936A1 (en) | 2004-09-13 | 2006-03-23 | Takeda Pharmaceutical Company Limited | Method and apparatus for producing oxidized compound |
| EP2264025A1 (en) | 2004-09-13 | 2010-12-22 | Takeda Pharmaceutical Company Limited | Method to produce a crystalline form of compounds (II') |
| US8747895B2 (en) | 2004-09-13 | 2014-06-10 | Aptalis Pharmatech, Inc. | Orally disintegrating tablets of atomoxetine |
| US10130580B2 (en) | 2004-10-12 | 2018-11-20 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| US10568832B2 (en) | 2004-10-12 | 2020-02-25 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| US9884014B2 (en) | 2004-10-12 | 2018-02-06 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| US11452689B2 (en) | 2004-10-12 | 2022-09-27 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| US10471017B2 (en) | 2004-10-21 | 2019-11-12 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions with gastrosoluble pore-formers |
| US10952971B2 (en) | 2004-10-21 | 2021-03-23 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions with gastrosoluble pore-formers |
| US9011926B2 (en) | 2005-02-25 | 2015-04-21 | Takeda Pharmaceutical Company Limited | Method for producing granules |
| EP2275088A2 (en) | 2005-02-25 | 2011-01-19 | Takeda Pharmaceutical Company Limited | Method for producing granules |
| US8871273B2 (en) | 2005-02-25 | 2014-10-28 | Takeda Pharmaceutical Company Limited | Method for producing granules |
| KR100771659B1 (en) | 2005-03-23 | 2007-10-30 | 주식회사 카이로제닉스 | Method of Preparing Pantoprazole and Its Intermediate |
| US11147772B2 (en) | 2005-05-02 | 2021-10-19 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US9566249B2 (en) | 2005-05-02 | 2017-02-14 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US10500161B2 (en) | 2005-05-02 | 2019-12-10 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US9579293B2 (en) | 2005-05-02 | 2017-02-28 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US9161918B2 (en) | 2005-05-02 | 2015-10-20 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US10045946B2 (en) | 2005-05-02 | 2018-08-14 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US9161919B2 (en) | 2005-05-02 | 2015-10-20 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| US20090030044A1 (en) * | 2005-06-07 | 2009-01-29 | Takeda Pharmaceutical Company Limited | Crystal of Salt of Benzimidazole Compound |
| WO2006132217A1 (en) | 2005-06-07 | 2006-12-14 | Takeda Pharmaceutical Company Limited | Crystal of salt of benzimidazole compound |
| US20090036406A1 (en) * | 2005-06-13 | 2009-02-05 | Takeda Pharmaceutical Company Limited | Injection |
| US20090209592A1 (en) * | 2005-10-06 | 2009-08-20 | Auspex Pharmaceuticals, Inc. | Inhibitors of the gastric h+, k+-atpase with enhanced therapeutic properties |
| US20070082929A1 (en) * | 2005-10-06 | 2007-04-12 | Gant Thomas G | Inhibitors of the gastric H+, K+-atpase with enhanced therapeutic properties |
| US7598273B2 (en) | 2005-10-06 | 2009-10-06 | Auspex Pharmaceuticals, Inc | Inhibitors of the gastric H+, K+-ATPase with enhanced therapeutic properties |
| US20090215831A1 (en) * | 2005-10-06 | 2009-08-27 | Auspex Pharmaceuticals, Inc. | Inhibitors of the gastric h+, k+-atpase with enhanced therapeutic properties |
| US20090306393A1 (en) * | 2005-12-17 | 2009-12-10 | Pliva Hrvatska D.O.O. | Process for preparing of, impurities free, substituted 2-benzimidazole-sulfoxide compound |
| US10064828B1 (en) | 2005-12-23 | 2018-09-04 | Intellipharmaceutics Corp. | Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems |
| WO2007074909A1 (en) | 2005-12-28 | 2007-07-05 | Takeda Pharmaceutical Company Limited | Controlled release solid preparation |
| US9561188B2 (en) | 2006-04-03 | 2017-02-07 | Intellipharmaceutics Corporation | Controlled release delivery device comprising an organosol coat |
| US9078827B2 (en) | 2006-05-12 | 2015-07-14 | Isa Odidi | Pharmaceutical composition having reduced abuse potential |
| US10632205B2 (en) | 2006-05-12 | 2020-04-28 | Intellipharmaceutics Corp | Pharmaceutical composition having reduced abuse potential |
| US10960077B2 (en) | 2006-05-12 | 2021-03-30 | Intellipharmaceutics Corp. | Abuse and alcohol resistant drug composition |
| US20100297226A1 (en) * | 2006-06-01 | 2010-11-25 | Dexcel Pharma Technologies Ltd. | Multiple unit pharmaceutical formulation |
| US7863330B2 (en) | 2006-06-14 | 2011-01-04 | Rottapharm S.P.A. | Deloxiglumide and proton pump inhibitor combination in the treatment of gastrointestinal disorders |
| US20110065797A1 (en) * | 2006-06-14 | 2011-03-17 | Rottapharm S.P.A | Deloxiglumide and proton pump inhibitors combination in the treatment of gastrointestinal disorders |
| US20100317689A1 (en) * | 2006-09-19 | 2010-12-16 | Garst Michael E | Prodrugs of proton pump inhibitors including the 1h-imidazo[4,5-b] pyridine moiety |
| US8129536B2 (en) | 2006-09-22 | 2012-03-06 | Orchid Chemicals & Pharmaceuticals Limited | Method for the purification of lansoprazole |
| US20100010230A1 (en) * | 2006-09-22 | 2010-01-14 | Orchid Chemicals & Pharmaceuticals Limited | Method for the purification of lansoprazole |
| WO2008067037A2 (en) | 2006-10-05 | 2008-06-05 | Santarus, Inc. | Novel formulations of proton pump inhibitors and methods of using these formulations |
| EP2486910A2 (en) | 2006-10-27 | 2012-08-15 | The Curators Of The University Of Missouri | Multi-chambered apparatus comprising a dispenser head |
| WO2008080092A2 (en) | 2006-12-22 | 2008-07-03 | Ironwood Pharmaceuticals, Inc. | Compositions comprising bile acid sequestrants for treating esophageal disorders |
| EP2478895A2 (en) | 2006-12-22 | 2012-07-25 | Ironwood Pharmaceuticals, Inc. | Compositions for treating esophageal disorders |
| EP2478894A2 (en) | 2006-12-22 | 2012-07-25 | Ironwood Pharmaceuticals, Inc. | Compositions for treating esophageal disorders |
| EP3628307A1 (en) | 2006-12-22 | 2020-04-01 | Ironwood Pharmaceuticals, Inc. | Compositions comprising bile acid sequestrants for treating esophageal disorders |
| WO2008081891A1 (en) | 2006-12-28 | 2008-07-10 | Takeda Pharmaceutical Company Limited | Orally disintegrating solid preparation |
| WO2008087665A2 (en) * | 2007-01-18 | 2008-07-24 | Matrix Laboratories Ltd | Process for preparation of lansoprazole |
| WO2008087665A3 (en) * | 2007-01-18 | 2011-01-27 | Matrix Laboratories Ltd | Process for preparation of lansoprazole |
| US20080194307A1 (en) * | 2007-02-13 | 2008-08-14 | Jeff Sanger | Sports-based game of chance |
| US20100210847A1 (en) * | 2007-07-17 | 2010-08-19 | Ranbaxy Laboratories Limited | Process for the preparation of pantoprazole sodium and pantoprazole sodium sesquihydrate |
| US8173158B2 (en) | 2007-10-12 | 2012-05-08 | Takeda Pharmaceuticals U.S.A., Inc. | Methods of treating gastrointestinal disorders independent of the intake of food |
| US20100280077A1 (en) * | 2007-12-18 | 2010-11-04 | Watson Pharma Private Limited | Process for Preparation of Stable Amorphous R-Lansoprazole |
| EP2292612A2 (en) | 2007-12-31 | 2011-03-09 | Takeda Pharmaceutical Company Limited | Crystalline solvated forms of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole |
| EP2573082A1 (en) | 2007-12-31 | 2013-03-27 | Takeda Pharmaceutical Company Limited | Crystalline solvated forms of (r)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1h-benzimidazole |
| WO2009105568A1 (en) | 2008-02-20 | 2009-08-27 | The Curators Of The University Of Missouri | Composition comprising a combination of omeprazole and lansoprazole, and a buffering agent, and methods of using same |
| US20100184807A1 (en) * | 2008-03-04 | 2010-07-22 | Bio-Quant, Inc. | Methods to inhibit tumor cell growth by using proton pump inhibitors |
| US20090227633A1 (en) * | 2008-03-04 | 2009-09-10 | Bassam Damaj | Methods to inhibit tumor cell growth by using proton pump inhibitors |
| US8222422B2 (en) | 2008-03-10 | 2012-07-17 | Takeda Pharmaceutical Company Limited | Crystal of benzimidazole compound |
| US20090263475A1 (en) * | 2008-04-21 | 2009-10-22 | Nagaraju Manne | Dexlansoprazole compositions |
| US8362042B2 (en) | 2008-05-14 | 2013-01-29 | Watson Pharma Private Limited | Stable R(+)-lansoprazole amine salt and a process for preparing the same |
| WO2010079504A2 (en) | 2008-05-14 | 2010-07-15 | Watson Pharma Private Limited | Stable r(+)-lansoprazole amine salt and a process for preparing the same |
| US20110065755A1 (en) * | 2008-05-14 | 2011-03-17 | Watson Pharma Private Limited | Stable r(+)-lansoprazole amine salt and a process for preparing the same |
| US20100113527A1 (en) * | 2008-09-30 | 2010-05-06 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of dexlansoprazole |
| US20100093747A1 (en) * | 2008-10-10 | 2010-04-15 | Erica Brook Goodhew | Method of inducing negative chemotaxis |
| US8778922B2 (en) | 2009-01-08 | 2014-07-15 | Lipocine Inc. | Steroidal compositions |
| US11304960B2 (en) | 2009-01-08 | 2022-04-19 | Chandrashekar Giliyar | Steroidal compositions |
| US8865695B2 (en) | 2009-01-08 | 2014-10-21 | Lipocine Inc. | Steroidal compositions |
| US11052096B2 (en) | 2009-01-08 | 2021-07-06 | Lipocine Inc. | Steroidal compositions |
| WO2010122583A2 (en) | 2009-04-24 | 2010-10-28 | Rubicon Research Private Limited | Oral pharmaceutical compositions of acid labile substances |
| WO2010134099A1 (en) | 2009-05-21 | 2010-11-25 | Cadila Healthcare Limited | One pot process for preparing omeprazole and related compounds |
| WO2011004387A2 (en) | 2009-06-18 | 2011-01-13 | Matrix Laboratories Ltd | Process for the preparation of dexlansoprazole polymorphic forms |
| US10729682B2 (en) | 2009-12-02 | 2020-08-04 | Adare Pharmaceuticals S.R.L. | Fexofenadine microcapsules and compositions containing them |
| US10166220B2 (en) | 2009-12-02 | 2019-01-01 | Adare Pharmaceuticals S.R.L. | Fexofenadine microcapsules and compositions containing them |
| US8580313B2 (en) | 2009-12-02 | 2013-11-12 | Aptalis Pharma Limited | Fexofenadine microcapsules and compositions containing them |
| US9233105B2 (en) | 2009-12-02 | 2016-01-12 | Adare Pharmaceuticals S.R.L. | Fexofenadine microcapsules and compositions containing them |
| US20110189271A1 (en) * | 2010-02-02 | 2011-08-04 | Vishal Lad | Pharmaceutical formulations of acid-labile drugs |
| WO2011138797A2 (en) | 2010-05-04 | 2011-11-10 | Cadila Healthcare Limited | Delayed release oral disintegrating pharmaceutical compositions of lansoprazole |
| WO2012001705A2 (en) | 2010-06-29 | 2012-01-05 | Cadila Healthcare Limited | Pharmaceutical compositions of (r)-lansoprazole |
| WO2012027331A1 (en) | 2010-08-27 | 2012-03-01 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| US10716794B2 (en) | 2010-11-30 | 2020-07-21 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9949985B2 (en) | 2010-11-30 | 2018-04-24 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US10799513B2 (en) | 2010-11-30 | 2020-10-13 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US10226473B2 (en) | 2010-11-30 | 2019-03-12 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US11364250B2 (en) | 2010-11-30 | 2022-06-21 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9943527B2 (en) | 2010-11-30 | 2018-04-17 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US11364249B2 (en) | 2010-11-30 | 2022-06-21 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US11311555B2 (en) | 2010-11-30 | 2022-04-26 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9205057B2 (en) | 2010-11-30 | 2015-12-08 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US11433083B2 (en) | 2010-11-30 | 2022-09-06 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9757390B2 (en) | 2010-11-30 | 2017-09-12 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US10881671B2 (en) | 2010-11-30 | 2021-01-05 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9034858B2 (en) | 2010-11-30 | 2015-05-19 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9358241B2 (en) | 2010-11-30 | 2016-06-07 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US10973833B2 (en) | 2010-11-30 | 2021-04-13 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9480690B2 (en) | 2010-11-30 | 2016-11-01 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| WO2012074110A1 (en) | 2010-12-03 | 2012-06-07 | 武田薬品工業株式会社 | Orally disintegrating tablet |
| US10561615B2 (en) | 2010-12-10 | 2020-02-18 | Lipocine Inc. | Testosterone undecanoate compositions |
| WO2012091153A2 (en) | 2010-12-27 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Orally disintegrating tablet |
| WO2012134828A1 (en) | 2011-03-25 | 2012-10-04 | Takeda Pharmaceuticals U.S.A., Inc. | Methods for treating heartburn and/or preventing gastric bleeding or hemorrhage in patients receiving clopidogrel therapy |
| WO2013081177A1 (en) | 2011-11-30 | 2013-06-06 | Takeda Pharmaceutical Company Limited | Dry coated tablet |
| WO2013088109A1 (en) | 2011-12-16 | 2013-06-20 | Oxagen Limited | Combination of crth2 antagonist and a proton pump inhibitor for the treatment of eosinophilic esophagitis |
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| WO2014113377A1 (en) | 2013-01-15 | 2014-07-24 | Ironwood Pharmaceuticals, Inc. | Gastro-retentive sustained-release oral dosage form of a bile acid sequestrant |
| EP3991719A1 (en) | 2013-01-15 | 2022-05-04 | Ironwood Pharmaceuticals, Inc. | Gastro-retentive sustained-release oral dosage form of a bile acid sequestrant |
| WO2014189034A1 (en) | 2013-05-21 | 2014-11-27 | 武田薬品工業株式会社 | Orally disintegrable tablet |
| US11273145B2 (en) | 2014-02-25 | 2022-03-15 | Muslim D. Shahid | Compositions and methods for the treatment of acid-related gastrointestinal disorders containing a dithiolane compound and a gastric acid secretion inhibitor |
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| WO2016126625A1 (en) | 2015-02-03 | 2016-08-11 | Ironwood Pharmaceuticals, Inc. | Methods of treating upper gastrointestinal disorders in ppi refractory gerd |
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